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US 2024/0174722 A1Published application
Synthetic signal peptides for directing secretion of heterologous proteins in yeast
AssigneeTenza, Inc.
InventorsAnik Debnath, Ameet Shetty
Life of this patent
Estimating the term…
Abstract
Provided herein are signal peptides that direct secretion of expressed payload proteins in yeast. Methods of using the signal peptides for therapeutic and non-therapeutic utilities are also provided. Compositions comprising yeast comprising the signal peptides and methods of using said yeast comprising the signal peptides for therapeutic and non-therapeutic utilities are also provided. Methods to design and generate the disclosed signal peptides are also provided.
Claims59
A pre-protein signal peptide comprising an amino acid sequence selected from the group consisting of Formula I, II, III, IV, V, IX, and XIII;
- wherein Formula I is represented as:
- A1-(A2)w-A3-(A4)x-(A5)y-A6-A7-A8-A9-A10-(A11)z (Formula I)
- wherein:
- w and x are each, independently, 1, 2, 3, 4, or 5;
- y is 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;
- and
- z is 1, 2, or 3;
- wherein:
- A1 is methionine;
- each A2 is, independently, a neutral or positively-charged amino acid with a hydropathy index of less than about 1;
- each A3, A5, A8, and A10 is each, independently, an amino acid with a hydropathy index greater than −1, excluding W and C;
- each A4 is, independently, a basic or neutral amino acid, excluding P, W, M, and C;
- A6 is an amino acid with a hydropathy index greater than −1, excluding W, M, and C;
- A7 is a non-aromatic amino acid with a hydropathy index of less than about 1.9 and an isoelectric point of about 5.4 to about 7.5, excluding P;
- A9 is an amino acid with a hydropathy index of greater than about −1.3;
- and
- each A11 is, independently, a neutral amino acid with a molecular weight of less than about 133 g/mol;
- wherein Formula II is represented as:
- B1-(B2)u-(B3)v-(B4)w-(B5)x-(B3)y-B7-B8-B9-B10-(B11)z (Formula II)
- wherein:
- u and w are each, independently, 0, 1, 2, or 3;
- v and z are each, independently, 1, 2, or 3;
- x is 0, 1, or 2;
- and
- y is 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;
- wherein:
- B1 is methionine;
- each B2, B4, B6, B8 and B10 is each, independently, an amino acid with a hydropathy index of greater than about −1, excluding W and C;
- each B3 is, independently, a positively-charged or polar amino acid with a hydropathy index of less than about 1;
- each B5 is, independently, a polar amino acid with a hydropathy index of greater than about −5 and less than about −0.5, or an amino acid with an isoelectric point of about 5 to about 11, excluding P, W, M, and C;
- each B7 and B11 is each, independently, a neutral amino acid with a molecular weight of less than about 133 g/mol;
- and
- B9 is an amino acid with a hydropathy index of greater than about −1.3;
- wherein Formula III is represented as:
- C1-(C2)r-(C3)t-(C4)u-[(C5)v-(C6)w]x-(C7)y-(C8)z-C9-C10-C11-[C12-C13]a (Formula III)
- wherein:
- r is 1, 2, or 3;
- t, u, y, and z are each, independently, 0, 1, 2, or 3;
- v and w are each, independently, 0, 1, or 2;
- a is 0 or 1;
- and
- x is 2, 3, 4, 5, 6, 7, 8, 9, or 10;
- wherein:
- C1 is methionine;
- each C2 is, independently, an amino acid having an isoelectric point of about 5.6 to about 10.8, a molecular weight of about 105 g/mol to about 175 g/mol, a hydropathy index of about −5.1 to about 0.6, and a helicity of about 0.8 to about 1;
- each C3, C5, C8, and C10 is each, independently, an amino acid having an isoelectric point of about 2.75 to about 10.8, a molecular weight of about 75 g/mol to about 205 g/mol, a hydropathy index of about −5.1 to about 34, and a helicity of about 0.5 to about 1.3;
- each C4 and C7 is each, independently, an amino acid having an isoelectric point of about 5 to about 10.8, a molecular weight of about 75 g/mol to about 205 g/mol, a hydropathy index of about −5.1 to about 34, and a helicity of about 0.5 to about 1.3;
- each C6, C9, C11, and C12 is each, independently, an amino acid having an isoelectric point of about 2.75 to about 9.8, a molecular weight of about 75 g/mol to about 205 g/mol;
- a hydropathy index of about −4 to about 34, and a helicity of about 0.5 to about 1.3;
- and
- C13 is an amino acid having an isoelectric point of about 5.6 to about 6.3, a molecular weight of about 105 g/mol to about 120 g/mol, a hydropathy index of about 0 to about 9.4, and a helicity of about 0.5 to about 1.1;
- wherein Formula IV is represented as:
- D1-(D2)q-(D3)r-(D4)t-(D5)u-[(D6)v-(D7)x-(D8)w-(D9)y]z-D10-Du-D12-[D13-D14]a (Formula IV)
- wherein:
- q is 1, 2, or 3;
- r, t, and u are each, independently, 0, 1, 2, or 3;
- v, w, x, and y are each, independently, 0, 1, or 2;
- a is 0 or 1;
- and
- z is 2, 3, 4, 5, 6, 7, 8, 9, or 10;
- wherein:
- D1 is methionine;
- each D2 is, independently, an amino acid having an isoelectric point of about 2.7 to about 10.8, a molecular weight of about 75 g/mol to about 205 g/mol, a hydropathy index of about −5.1 to about 34, and a helicity of about 0.5 to about 1.3;
- each D3 is, independently, an amino acid having an isoelectric point of about 5 to about 10.8, a molecular weight of about 89 g/mol to about 205 g/mol, a hydropathy index of about −4 to about 34, and a helicity of about 0.5 to about 1.3;
- each D4, D9 and D11 is each, independently an amino acid having an isoelectric point of about 2.7 to about 10.8, a molecular weight of about 75 g/mol to about 205 g/mol, a hydropathy index of about −5.1 to about 34, and a helicity of about 0.5 to about 1.3;
- each D5 is, independently, an amino acid having an isoelectric point of about 3.2 to about 10.8, a molecular weight of about 75 g/mol to about 205 g/mol, a hydropathy index of about −5.1 to about 34, and a helicity of about 0.75 to about 1.3;
- each D6 is, independently, an amino acid having an isoelectric point from about 5 to about 10.8, a molecular weight of about 75 g/mol to about 205 g/mol, a hydropathy index of about −5.1 to about 34, and a helicity of about 0.5 to about 1.3;
- each D7 is, independently, an amino acid having an isoelectric point of about 5.4 to about 6.1, a molecular weight of about 117 g/mol to about 205 g/mol, a hydropathy index of about 2.5 to about 34, and a helicity of about 1 to about 1.3;
- each D8, D10, D12, and D13 is each, independently, an amino acid having an isoelectric point of about 2.7 to about 10.8, a molecular weight of about 75 g/mol to about 182 g/mol, a hydropathy index of about −5.1 to about 32, and a helicity of about 0.75 to about 1.3;
- and
- D14 is an amino acid with an isoelectric point of about 2.7 to about 10.8, a molecular weight of about 75 g/mol to about 182 g/mol, a hydropathy index of about −5.1 to about 32, and a helicity of about 0.5 to about 1.3;
- wherein Formula V is represented as:
- E1-[(E2)i-(E3)j-(E4)q]r-(E5)t-(E6)u-(E7)v-[(E8)w-(E9)x]y-(E10)z-E11-E12-E13-[E14-E15]a (Formula V)
- wherein:
- i, j, q, w, x and a are each, independently, 0 or 1;
- r is 1, 2, or 3;
- t, u, v, and z are each, independently, 0, 1, 2, or 3;
- and
- y is 2, 3, 4, 5, 6, 7, 8, 9, or 10;
- wherein:
- E1 is methionine;
- each E2 is, independently, an amino acid having an isoelectric point of about 3.2 to about 10.8, a molecular weight of about 105 g/mol to about 175 g/mol, a hydropathy index of about −4 to about 1, and a helicity of about 0.85 to about 1;
- each E3 is, independently, an amino acid having an isoelectric point of about 2.7 to about 10.8, a molecular weight of about 75.1 g/mol to about 205 g/mol, a hydropathy index of about −5.1 to about 33.5, and a helicity of about 0.57 to about 1.3;
- each E4 is, independently, an amino acid having an isoelectric point of about 5 to about 10.8, a molecular weight of about 105 g/mol to about 205 g/mol, a hydropathy index of about −5.1 to about 33.5, and a helicity of about 0.57 to about 1.3;
- each E5 and E8 is each, independently, an amino acid having an isoelectric point of about 2.7 to about 10.8, a molecular weight of about 75 g/mol to about 205 g/mol, a hydropathy index of about −5.1 to about 33.5, and a helicity of about 0.57 to about 1.3;
- each E6 is, independently, an amino acid having an isoelectric point of about 5 to about 10.8, a molecular weight of about 89 g/mol to about 205 g/mol, a hydropathy index of about −5.1 to about 33.5, and a helicity of about 0.57 to about 1.3;
- each E7 is, independently, an amino acid having an isoelectric point of about 5 to about 9.75, a molecular weight of about 75 g/mol to about 205 g/mol, a hydropathy index of about −4 to about 33.5, and a helicity of about 0.79 to about 1.3;
- each E9, E13, and E14 is each, independently, an amino acid having an isoelectric point of about 2.7 to about 10.8, a molecular weight of about 75 g/mol to about 205 g/mol, a hydropathy index of about −5.1 to about 33.5, and a helicity of about 0.57 to about 1.3;
- each E10 and E12 is, independently, an amino acid having an isoelectric point of about 5 to about 10.8, a molecular weight of about 75 g/mol to about 205 g/mol, a hydropathy index of about −5.1 to about 34, and a helicity of about 0.5 to about 1.3;
- E11 is an amino acid having an isoelectric point of about 5 to about 9.75, a molecular weight of about 89 g/mol to about 205 g/mol, a hydropathy index of about −4 to about 33.5, and a helicity of about 0.79 to about 1.3;
- and
- E15 is an amino acid having an isoelectric point of about 2.7 to about 10.8, a molecular weight of about 75 g/mol to about 205 g/mol, a hydropathy index of about −4 to about 15.5, and a helicity of about 0.57 to about 1.2;
- wherein Formula IX is represented as:
- F1-(F2)v-(F3)w-[(F4)x-(F5)y]z-F6-F7-F8-[F9-F10]a (Formula IX)
- wherein:
- v and w are each, independently, 0, 1, 2, or 3;
- x and y are each, independently, 0, 1, 2, 3, or 4;
- a is 0 or 1;
- and
- z is 1, 2, 3, 4, 5, 6, 7, or 8;
- wherein:
- F1 is an amino acid having an isoelectric point of about 5.4 to about 11, a molecular weight of about 89 g/mol to about 175 g/mol;
- a hydropathy index of about −4 to about 31, and a helicity or about 0.9 to about 1.3;
- each F2 is, independently, an amino acid having an isoelectric point of about 3 to about 11, a molecular weight of about 89 g/mol to about 205 g/mol;
- a hydropathy index of about −5.1 to about 34, and a helicity or about 0.5 to about 1.3;
- each F3 and F7 is each, independently, an amino acid having an isoelectric point of about 3 to about 11, a molecular weight of about 89 g/mol to about 205 g/mol;
- a hydropathy index of about −5.1 to about 34, and a helicity or about 0.5 to about 1.3;
- each F4 is, independently, an amino acid having an isoelectric point of about 3 to about 11, a molecular weight of about 89 g/mol to about 205 g/mol;
- a hydropathy index of about −5.1 to about 34, and a helicity or about 0.5 to about 1.3;
- each F5, F6, F8, and F9 is each, independently, an amino acid having an isoelectric point of about 3 to about 11, a molecular weight of about 89 g/mol to about 205 g/mol;
- a hydropathy index of about −5.1 to about 34, and a helicity or about 0.5 to about 1.3;
- and
- F10 is an amino acid having an isoelectric point of about 3 to about 11, a molecular weight of about 89 g/mol to about 205 g/mol;
- a hydropathy index of about −5.1 to about 34, and a helicity or about 0.5 to about 1.3;
- and
- wherein Formula XIII is represented as:
- L1-(L2)x[(L3)a-(L4)a]y-[(L5)a-(L6)a-(L7)a]z-(L8)a-(L9)a-(L10)a-(L11)a-(L12)a (Formula XIII)
- wherein:
- x is 1, 2, or 3;
- y is 1, 2, 3, or 4;
- z is 5, 6, 7, 8, 9, or 10;
- and
- each a is, independently, 0 or 1;
- wherein:
- each L2 is, independently, an amino acid having an isoelectric point of about 2.7 to about 10.8, a molecular weight of about 75 g/mol to about 205 g/mol;
- a hydropathy index of about −5.1 to about 34, and a helicity or about 0.5 to about 1.3;
- each L3 and L6 is each, independently, an amino acid having an isoelectric point of about 2.7 to about 10.8, a molecular weight of about 75 g/mol to about 205 g/mol;
- a hydropathy index of about −5.1 to about 34, and a helicity or about 0.5 to about 1.3;
- each L4, L7 and L9 is each, independently, an amino acid having an isoelectric point of about 2.7 to about 10.8, a molecular weight of about 75 g/mol to about 205 g/mol;
- a hydropathy index of about −5.1 to about 34, and a helicity or about 0.5 to about 1.3;
- each L5, L8, L10 and Ln is each, independently, an amino acid having an isoelectric point of about 2.7 to about 10.8, a molecular weight of about 75 g/mol to about 205 g/mol;
- a hydropathy index of about −5.1 to about 34, and a helicity or about 0.5 to about 1.3;
- and
- L12 is an amino acid having an isoelectric point of about 2.7 to about 10.8, a molecular weight of about 75 g/mol to about 205 g/mol;
- a hydropathy index of about −5.1 to about 34, and a helicity or about 0.5 to about 1.3.
132 more elements
A pre-protein signal peptide comprising an amino acid sequence having at least 90%, 910%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 28, 31, 32, 33, 55, 70, 71, 72, or 73.
A pro-protein signal peptide comprising an amino acid sequence selected from the group consisting of Formula VI, VII, VIII, X, XI, XIV, and XV;
- wherein Formula VI is represented as:
- G1-G2-G3-G4-G5-G6-G7-G8-G9-G10-G11-G12-G13-G14-G15-G16-G17-G18-G19-G20-G21-G22-G23-G24-G25 (Formula VI)
- wherein:
- G1 is an amino acid selected from the group consisting of I, L, F, V, A, N, S, D, R, and K;
- G2 is an amino acid selected from the group consisting of P, S, N, G, and E;
- G3 is an amino acid selected from the group consisting of L, F, I, V, Y, A, S, R, and H;
- G4 is an amino acid selected from the group consisting of V, M, P, Y, A, T, S, N, K, and H;
- G5 is an amino acid selected from the group consisting of A, G, R, Y, K, D, M, V, W, I, and L;
- G6 is an amino acid selected from the group consisting of N, R, and K;
- G7 is an amino acid selected from the group consisting of V, P, A, T, Q, G, E, D, R, and K;
- G8 is an amino acid selected from the group consisting of P, Y, T, Q, S, N, W, F, R, K, and H;
- G9 is an amino acid selected from the group consisting of F, L, A, Q, N, S, E, G, D, and H;
- G10 is an amino acid selected from the group consisting of H, S, N, D, Q, E, T, Y, M, V, I, and L;
- G11 is an amino acid selected from the group consisting of S, R, T, G, K, E, D, and P;
- G12 is an amino acid selected from the group consisting of D, E, Q, N, A, and V;
- G13 is an amino acid selected from the group consisting of N, S, E, D, T, H, K, A, and P;
- G14 is an amino acid selected from the group consisting of G, S, N, H, E, C, Y, L, and F;
- G15 is an amino acid selected from the group consisting of S, T, and H;
- G16 is an amino acid selected from the group consisting of E, D, Q, N, S, T, K, and A;
- G17 is an amino acid selected from the group consisting of W, N, D, and R;
- G18 is an amino acid selected from the group consisting of L and F;
- G19 is an amino acid selected from the group consisting of Y, V, A, Q, N, S, E, D, L, R, K, and H;
- G20 is an amino acid selected from the group consisting of K, R, S, and I;
- G21 is R;
- G22 is an amino acid selected from the group consisting of D, E, N, S, T, G, A, Y, and L;
- G23 and G24 are each, independently, an amino acid selected from the group consisting of V, P, Y, I, A, E, K, F, T, S, G, D, M, and N;
- and
- G25 is an amino acid selected from the group consisting of Y, P, A, T, Q, S, E, F, and H;
- wherein Formula VII is represented as:
- (H1)m-(H2)m-(H3)m-(H4)m-(H5)m-(H6)m-(H7)m-(H8)m-(H9)m-(H10)m-(H11)m- (H12)m-(H13)m-(H14)m-(H15)m-(H16)m-(H17)m-(H18)m-(H19)m-(H20)m-(H21)m-(H22)m-(H23)m-(H24)m-(H25)m-(H26)m-(H27)m-(H28)m-(H29)m-(H30)m-(H31)m-(H32)m-(H33)m-(H34)m-(H35)m-(H36)m-H37-H38-H39-H40 (Formula VII)
- wherein:
- each m is, independently, 0, 1, or 2;
- wherein:
- each H1 is, independently, an amino acid selected from the group consisting of E, D, S, L, G, Q, and A;
- each H2 and H28 is each, independently, an amino acid selected from the group consisting of P, S, R, T, N, G, D, K, and A;
- each H3 is, independently, an amino acid selected from the group consisting of W and Y;
- each H4 is, independently, an amino acid selected from the group consisting of S, N, A, P, and V;
- each H5 and H30 is each, independently, an amino acid selected from the group consisting of T, Q, A, E, F, and S;
- each H6 is, independently, an amino acid selected from the group consisting of L, F, and I;
- each H7 is, independently, an amino acid selected from the group consisting of F, V, M, T, S, and K;
- each H8 is, independently, an amino acid selected from the group consisting of V, P, I, A, S, and K;
- each H9 and H17 is each, independently, an amino acid selected from the group consisting of T, G, V, W, and A;
- each H10 is, independently, an amino acid selected from the group consisting of R, H, S, G, N, E, T, and V;
- each H11 is, independently, an amino acid selected from the group consisting of S, G, D, A, and M;
- each H12 is, independently, an amino acid selected from the group consisting of T, S, E, G, D, K, and H;
- each H13 is, independently, an amino acid selected from the group consisting of L, M, Y, N, S, D, and K;
- each H14 is, independently, an amino acid selected from the group consisting of D, Q, N, S, K, and C;
- each H15 is, independently, an amino acid selected from the group consisting of E, S, D, L, and G;
- each H16 is, independently, an amino acid selected from the group consisting of I, L, V, M, A, and T;
- each H18 is, independently, an amino acid selected from the group consisting of D, E, S, T, K, and G;
- each H19 is, independently, an amino acid selected from the group consisting of Y, F, and L;
- each H20 is, independently, an amino acid selected from the group consisting of N, Q, S, T, R, and F;
- each H21 and H34 is each, independently, an amino acid selected from the group consisting of S, K, T, A, Y, M, and F;
- each H22 is, independently, an amino acid selected from the group consisting of T, Q, S, D, C, V, and L;
- each H23 is, independently, an amino acid selected from the group consisting of G, S, K, N, H, D, W, and L;
- each H24 is, independently, an amino acid selected from the group consisting of I, L, V, P, N, and E;
- each H25 and H33 is each, independently, an amino acid selected from the group consisting of A, T, G, R, Y, L, F, and E;
- each H26 and H40 is each, independently, an amino acid selected from the group consisting of V, I, F, M, L, A, and T;
- each H27 is, independently, an amino acid selected from the group consisting of D, E, Q, N, S, A, and I;
- each H29 is, independently, an amino acid selected from the group consisting of E, D, T, A, Y, M, V, I, F, and L;
- each H31 is, independently, an amino acid selected from the group consisting of F, W, V, M, S, G, and R;
- each H32 is, independently, an amino acid selected from the group consisting of H, S, E, G, and T;
- each H35 is, independently, an amino acid selected from the group consisting of R, K, S, and Q;
- each H36 is, independently, an amino acid selected from the group consisting of H, R, S, T, A, V, W, and L;
- H37 is an amino acid selected from the group consisting of K, Q, D, A, and I;
- H38 is an amino acid selected from the group consisting of R, K, T, and F;
- and
- H39 is an amino acid selected from the group consisting of D, N, S, T, K, A, Y, and L;
- wherein Formula VIII is represented as:
- (I1)m-(I2)m-(I3)m-(I4)m-(I5)m-(I6)m-(I7)x-(I8)m-(I9)m-(I10)m-(I11)x- (I12)m-(I13)x-(I14)x-(I15)m-(I16)x-(I17)m-I18-I19-I20-I21-I22-I23 (Formula VIII)
- wherein:
- each m is, independently, 0, 1, or 2;
- and
- each x is, independently, 0, 1, 2, 3, or 4;
- wherein:
- each I1 and I6 is each, independently, an amino acid selected from the group consisting of S, Q, E, A, I, G, V, R, T, and Y;
- each I2 is, independently, an amino acid selected from the group consisting of T, S, E, R, P, V, I, and F;
- each I3 is, independently, L.
- each I4 is, independently, an amino acid selected from the group consisting of T, N, K, and M;
- each I5 is, independently, an amino acid selected from the group consisting of P, A, and D;
- each I7 is, independently, an amino acid selected from the group consisting of T, S, K, H, Y, V, and F;
- each I8 and I15 is each, independently, an amino acid selected from the group consisting of F, L, W, A, T, M, Y, and C;
- each I9 is, independently, an amino acid selected from the group consisting of I, L, and V;
- each I10 and I16 is each, independently, an amino acid selected from the group consisting of G, S, N, E, D, A, K, H, C, P, and F;
- each I11 is, independently, an amino acid selected from the group consisting of I, L, V, A, T, and S;
- each I12 is, independently, an amino acid selected from the group consisting of T, N, A, E, and G;
- each I13 is, independently, an amino acid selected from the group consisting of E, Q, S, T, R, K, A, L, D, and F;
- each I14 is, independently, an amino acid selected from the group consisting of T, S, Q, F, A, G, V, I, and L;
- each I17 is, independently, an amino acid selected from the group consisting of I, L, V, N, A, T, and S;
- I18 and I21 are each, independently, an amino acid selected from the group consisting of R, K, Q, and A;
- I19 is an amino acid selected from the group consisting of H, R, S, N, T, A, V, and W;
- I20 is an amino acid selected from the group consisting of K, N, Q, D, E, A, and I;
- I22 is an amino acid selected from the group consisting of D, N, S, A, Y, and L;
- and
- I23 is an amino acid selected from the group consisting of V, I, L, F, and A;
- wherein Formula X is represented as:
- (J1)z-(J2)z-(J3)z-(J4)z-(J5)z-(J6)z-(J7)z-(J8)z-(J9)z-(J10)z-(J11)z- (J12)z-(J13)z-(J14)z-(J15)z-(J16)z-(J17)z-(J18)z-(J19)z-(J20)z-(J21)z-J22-J23-J24-J25 (Formula X)
- wherein:
- each z is, independently, 0, 1, 2, 3, 4, or 5;
- wherein:
- each J1 is, independently, an amino acid selected from the group consisting of H, K, G, A, P, F, and L;
- each J2 is, independently, an amino acid selected from the group consisting of D, E, N, G, P, H, T, R, K, and A;
- each J3 is, independently, an amino acid selected from the group consisting of G, A, P, V, and L;
- each J4 is, independently, an amino acid selected from the group consisting of F, I, P, A, S, E, D, R, and K;
- each J5 is, independently, an amino acid selected from the group consisting of S, R, T, G, K, E, D, and C;
- each J6 is, independently, an amino acid selected from the group consisting of T, S, A, D, and F;
- each J7 is, independently, an amino acid selected from the group consisting of D, E, N, G, P, H, T, R, K, and A;
- each J8 is, independently, an amino acid selected from the group consisting of Y, C, A, W, I, S, E, D, F, L, R, and K;
- each J9 is, independently, an amino acid selected from the group consisting of H, K, N, D, G, T, A, C, Y, V, and L;
- each J10 is, independently, an amino acid selected from the group consisting of L, V, A, G, E, I, P, and R;
- each J11 is, independently, an amino acid selected from the group consisting of I, W, V, Y, P, T, N, S, R, and K;
- each J12 is, independently, an amino acid selected from the group consisting of A, G, Q, N, R, Y, E, D, and L;
- each J13 is, independently, an amino acid selected from the group consisting of I, L, W, V, M, Y, P, A, S, and G;
- each J14 is, independently, an amino acid selected from the group consisting of V, C, L, F, A, T, N, G, and R;
- each J15 is, independently, an amino acid selected from the group consisting of G, S, R, K, A, T, H, E, W, L, and F;
- each J16 is, independently, an amino acid selected from the group consisting of D, E, Q, S, H, T, R, G, Y, V, F, and L;
- each J17 is, independently, an amino acid selected from the group consisting of E, S, G, Y, I, and L;
- each J18 is, independently, an amino acid selected from the group consisting of A, S, P, H, and V;
- each J19 is, independently, an amino acid selected from the group consisting of N, E, R, K, and A;
- each J20 is, independently, an amino acid selected from the group consisting of R, T, V, I, and L;
- each J21 is, independently, an amino acid selected from the group consisting of L, V, A, G, E, I, P, and R;
- J22 is an amino acid selected from the group consisting of K, R, D, T, M, and W;
- J23 is an amino acid selected from the group consisting of R, T, V, I, and L;
- J24 is an amino acid selected from the group consisting of S, N, G, E, D, P, and W;
- and
- J25 is an amino acid selected from the group consisting of A, T, S, Y, M, V, and L;
- wherein Formula XI is represented as:
- (K1)b-(K2)b-(K3)b-(K4)b-(K5)b-(K6)b-(K7)b-(K8)b-(K9)b-(K10)b-(K11)b- (K12)b-(K13)b-(K14)b-(K15)b-(K16)b-(K17)b-(K18)b-(K19)b-(K20)b-(K21)b-(K22)b-(K23)b-(K24)b-(K25)b-(K26)b-(K27)b-(K28)b-(K29)b-(K30)b-(K31)b-(K32)b-(K33)b-(K34)b-(K35)b-(K36)b-(K37)b-(K38)b-(K39)b-(K40)b-(K41)b-(K42)b-(K43)b-(K44)b-(K45)b-(K46)b-(K47)b-(K48)b-(K49)b-(K50)b-(K51)b-(K52)b-(K53)b-(K54)b-(K55)b-(K56)b-(K57)b-(K58)b-(K59)b-(K60)b-(K61)b-(K62)b-(K63)b-(K64)b-(K65)b-(K66)b-(K67)b-(K68)b-(K69)b-(K70)b-(K71)b-(K72)b-(K73)b-(K74)b-(K75)b-(K76)b-(K77)b-(K78)b-(K79)b-(K80)b-(K81)b-(K82)b-(K83)b-(K84)b-(K85)b-(K86)b-(K87)b-(K88)b-K89-K89-K89-K89-K89 (Formula XI)
- wherein:
- each b is, independently, 0, 1, 2, or 3;
- wherein:
- each K1 is, independently, an amino acid selected from the group consisting of S, G, D, A, C, P, and Y;
- each K2 is, independently, an amino acid selected from the group consisting of Q, S, E, T, R, K, G, A, Y, M, V, and I;
- each K3 is, independently, an amino acid selected from the group consisting of G, S, N, T, Q, D, P, L, F, V, K, A, and C;
- each K4 is, independently, an amino acid selected from the group consisting of R, G, N, D, A, P, Y, and L;
- each K5 is, independently, an amino acid selected from the group consisting of E, A, V, Q, G, Y, M, I, and L;
- each K6 is, independently, an amino acid selected from the group consisting of S, Q, R, T, D, G, E, A, and K;
- each K7 is, independently, an amino acid selected from the group consisting of N, Q, R, H, K, A, I, F, and L;
- each K8 is, independently, an amino acid selected from the group consisting of A, T, Q, G, R, K, D, L, F, C, V, S, and H;
- each K9 is, independently, an amino acid selected from the group consisting of G, S, N, T, Q, D, P, L, F, V, K, A, and C;
- each K10 is, independently, an amino acid selected from the group consisting of K, H, E, A, Y, L, and F;
- each K11 is, independently, an amino acid selected from the group consisting of S, T, K, E, A, C, W, F, and L;
- each K12 is, independently, an amino acid selected from the group consisting of K, R, H, S, Q, D, E, and A;
- each K13 is, independently, an amino acid selected from the group consisting of G, S, T, E, P, W, R, N, and Q;
- each K14 is, independently, an amino acid selected from the group consisting of D, Q, S, G, V, E, N, H, R, P, and F;
- each K15 is, independently, an amino acid selected from the group consisting of C, A, M, V, S, E, G, I, F, and L;
- each K16 is, independently, an amino acid selected from the group consisting of R, K, S, Q, T, Y, N, V, I, L, and C;
- each K17 is, independently, an amino acid selected from the group consisting of A, G, S, Q, Y, E, D, H, and I;
- each K18 is, independently, an amino acid selected from the group consisting of R, K, S, Q, T, Y, N, V, I, L, and C;
- each K19 is, independently, an amino acid selected from the group consisting of E, D, T, H, K, G, P, V, and L;
- each K20 is, independently, an amino acid selected from the group consisting of F, L, I, V, M, T, G, and R;
- each K21 is, independently, an amino acid selected from the group consisting of E, D, S, G, A, C, and P;
- each K22 is, independently, an amino acid selected from the group consisting of D, T, G, A, Y, N, S, C, P, W, and I;
- each K23 is, independently, an amino acid selected from the group consisting of G, S, N, E, D, Y, and L;
- each K24 is, independently, an amino acid selected from the group consisting of T, S, E, G, P, and I;
- each K25 is, independently, an amino acid selected from the group consisting of K, S, G, T, and L;
- each K26 is, independently, an amino acid selected from the group consisting of S, G, K, E, D, P, and F;
- each K27 is, independently, an amino acid selected from the group consisting of P, A, E, L, T, Q, S, G, K, Y, F, C, V, W, and R;
- each K28 is, independently, an amino acid selected from the group consisting of E, D, Q, S, T, P, and L;
- each K29 is, independently, an amino acid selected from the group consisting of A, T, S, E, V, W, and I;
- each K30 is, independently, an amino acid selected from the group consisting of K, H, S, G, N, Q, P, and Y;
- each K31 is, independently, an amino acid selected from the group consisting of L, F, V, P, A, N, G, and H;
- each K32 is, independently, an amino acid selected from the group consisting of A, G, N, P, R, E, and K;
- each K33 is, independently, an amino acid selected from the group consisting of R, S, N, A, P, Y, V, I, F, and G;
- each K34 is, independently, an amino acid selected from the group consisting of E, S, T, V, I, H, A, P, F, and L;
- each K35 is, independently, an amino acid selected from the group consisting of A, T, Q, P, R, V, N, E, and L;
- each K36 is, independently, an amino acid selected from the group consisting of R, K, H, G, Q, D, T, Y, and F;
- each K37 is, independently, an amino acid selected from the group consisting of D, E, N, T, C, Y, V, I, and L;
- each K38 is, independently, an amino acid selected from the group consisting of S, Q, R, T, D, G, E, A, and K;
- each K39 is, independently, an amino acid selected from the group consisting of K, S, G, Q, D, E, A, M, I, and L;
- each K40 is, independently, an amino acid selected from the group consisting of H, K, S, D, E, T, P, and L;
- each K41 is, independently, an amino acid selected from the group consisting of A, T, S, N, P, V, L, and F;
- each K42 is, independently, an amino acid selected from the group consisting of K, D, M, V, I, L, and F;
- each K43 is, independently, an amino acid selected from the group consisting of G, S, N, T, Q, D, P, L, F, V, K, A, and C;
- each K44 is, independently, an amino acid selected from the group consisting of L, T, F, V, P, A, K, and I;
- each K45 is, independently, an amino acid selected from the group consisting of G, S, K, N, T, Q, D, A, P, L, F, and V;
- each K46 is, independently, an amino acid selected from the group consisting of L, F, Q, S, G, and D;
- each K47 is, independently, an amino acid selected from the group consisting of S, R, E, A, P, V, W, and L;
- each K48 is, independently, an amino acid selected from the group consisting of A, S, V, G, Q, R, E, D, L, T, K, F, C, and H;
- each K49 is, independently, an amino acid selected from the group consisting of E, S, T, R, G, A, P, and L;
- each K50 is, independently, an amino acid selected from the group consisting of S, N, R, A, P, and Y;
- each K51 is, independently, an amino acid selected from the group consisting of G, A, T, H, M, V, L, and F;
- each K52 is, independently, an amino acid selected from the group consisting of S, T, H, A, C, M, and L;
- each K53 is, independently, an amino acid selected from the group consisting of G, S, T, E, P, W, R, N, and Q;
- each K54 is, independently, an amino acid selected from the group consisting of S, H, Y, F, N, Q, R, T, G, and K;
- each K55 is, independently, an amino acid selected from the group consisting of A, T, Q, E, M, V, I, L, and F;
- each K56 is, independently, an amino acid selected from the group consisting of S, N, E, A, P, F, and L;
- each K57 is, independently, an amino acid selected from the group consisting of D, S, R, K, A, V, W, I, and F;
- each K58 is, independently, an amino acid selected from the group consisting of K, S, G, D, T, L, R, E, Y, and N;
- each K59 is, independently, an amino acid selected from the group consisting of S, R, G, A, V, and F;
- each K60 is, independently, an amino acid selected from the group consisting of A, T, Q, G, R, K, D, L, F, C, V, S, and H;
- each K61 is, independently, an amino acid selected from the group consisting of R, S, G, N, E, T, A, and V;
- each K62 is, independently, an amino acid selected from the group consisting of E, S, T, V, I, H, A, P, F, and L;
- each K63 is, independently, an amino acid selected from the group consisting of A, G, S, Q, R, E, D, V, L, T, K, F, C, and H;
- each K64 is, independently, an amino acid selected from the group consisting of E, A, V, Q, G, Y, M, I, and L;
- each K65 is, independently, an amino acid selected from the group consisting of G, S, T, E, P, W, R, N, and Q;
- each K66 is, independently, an amino acid selected from the group consisting of A, G, P, M, N, V, and S;
- each K67 is, independently, an amino acid selected from the group consisting of T, Q, E, N, S, A, Y, V, W, and F;
- each K68 is, independently, an amino acid selected from the group consisting of I, V, P, and A;
- each K69 is, independently, an amino acid selected from the group consisting of D, Q, S, G, V, E, N, H, R, P, and F;
- each K70 is, independently, an amino acid selected from the group consisting of G, S, R, N, T, Y, L, and F;
- each K71 is, independently, an amino acid selected from the group consisting of E, D, N, S, T, H, and Y;
- each K72 is, independently, an amino acid selected from the group consisting of L, I, W, V, A, T, S, E, R, and K;
- each K73 is, independently, an amino acid selected from the group consisting of G, S, K, A, C, F, N, T, Q, D, P, L, and V;
- each K74 is, independently, an amino acid selected from the group consisting of A, S, N, P, K, V, I, and L;
- each K75 is, independently, an amino acid selected from the group consisting of P, A, E, L, T, Q, S, G, K, Y, F, C, V, W, and R;
- each K76 is, independently, an amino acid selected from the group consisting of L, T, F, V, P, A, K, and I;
- each K77 is, independently, an amino acid selected from the group consisting of M, V, Y, L, A, N, E, and H;
- each K78 is, independently, an amino acid selected from the group consisting of D, T, G, A, Y, N, S, C, P, W, and I;
- each K79 is, independently, an amino acid selected from the group consisting of A, S, V, G, Q, R, E, D, L, T, K, F, C, and H;
- each K80 is, independently, an amino acid selected from the group consisting of K, R, S, A, P, V, I, and L;
- each K81 is, independently, an amino acid selected from the group consisting of F, L, V, A, T, S, E, D, R, and K;
- each K82 is, independently, an amino acid selected from the group consisting of L, F, M, A, N, G, and E;
- each K83 is, independently, an amino acid selected from the group consisting of D, S, H, A, V, I, F, and L;
- each K84 is, independently, an amino acid selected from the group consisting of A, T, Q, S, R, V, L, G, H, F, K, D, and C;
- each K85 is, independently, an amino acid selected from the group consisting of T, Q, E, N, S, A, Y, V, W, and F;
- each K86 is, independently, an amino acid selected from the group consisting of A, P, R, Y, K, D, M, L, and F;
- each K87 is, independently, an amino acid selected from the group consisting of N, S, D, T, A, P, and L;
- each K88 is, independently, an amino acid selected from the group consisting of R, S, N, A, P, Y, V, I, F, and G;
- K89 is an amino acid selected from the group consisting of K, R, H, G, E, T, Y, and I;
- K90 is an amino acid selected from the group consisting of R, S, G, N, Q, A, Y, and W;
- K91 is an amino acid selected from the group consisting of V, I, and F;
- K92 is an amino acid selected from the group consisting of A, G, P, M, N, V, and S;
- and
- K93 is an amino acid selected from the group consisting of E, D, Q, S, R, K, M, and L;
- wherein Formula XIV is represented as:
- (M1)b-(M2)b-(M3)b-(M4)b-(M5)b-(M6)b-(M7)b-(M8)b-(M9)b-(M10)b-(M11)b- (M12)b-(M13)b-(M14)b-(M15)b-(M16)b-(M17)b-(M18)b-(M19)b-(M20)b-(M21)b-(M22)b-(M23)b-(M24)b-(M25)b-(M26)b-(M27)b-(M28)b-(M29)b-(M30)b-(M31)b-(M32)b-(M33)b-(M34)b-(M35)b-(M36)b-(M37)b-(M38)b-(M39)b-(M40)b-(M41)b-(M42)b-(M43)b-(M44)b-(M45)b-(M46)b-(M47)b-(M48)b-(M49)b-(M50)b-(M51)b-(M52)b-(M53)b-(M54)b-(M55)b-(M56)b-(M57)b-(M58)b-(M59)b-(M60)b-(M61)b-(M62)b-(M63)b-(M64)b-(M65)b-(M66)b-(M67)c-(M68)c-(M69)c-(M70), (Formula XIV);
- wherein:
- each b is, independently, 0, 1, 2, or 3;
- and
- each c is, independently, 1 or 2;
- wherein:
- each M1 is, independently, an amino acid selected from the group consisting of A, T, C, S, Y, E, H, V, W, I, L, F, G, Q, N, P, R, K, D, and M;
- each M2 is, independently, an amino acid selected from the group consisting of S, T, A, N, R, G, E, P, V, F, L, Q, K, H, D, I, C, Y, M, and W;
- each M3 is, independently, an amino acid selected from the group consisting of G, S, R, A, T, Q, E, D, C, Y, V, I, L, and N;
- each M4 is, independently, an amino acid selected from the group consisting of R, H, N, Q, E, A, Y, M, V, W, F, and L;
- each M5 is, independently, an amino acid selected from the group consisting of P, Y, A, T, Q, S, G, D, R, K, C, V, I, L, and H;
- each M6 is, independently, an amino acid selected from the group consisting of T, Q, N, S, A, E, G, D, H, P, F, L, C, K, V, R, Y, I, M, and W;
- each M7 is, independently, an amino acid selected from the group consisting of A, G, S, Q, N, K, D, T, C, Y, E, H, V, W, I, L, F, P, R, and M;
- each M8 is, independently, an amino acid selected from the group consisting of T, Q, N, S, A, G, C, R, K, P, Y, M, V, I, L, F, E, W, D, and H;
- each M9 is, independently, an amino acid selected from the group consisting of G, S, H, P, R, A, T, Q, E, D, C, Y, V, I, L, N, W, F, K, and M;
- each M10 is, independently, an amino acid selected from the group consisting of Q, E, and W;
- each M11 is, independently, an amino acid selected from the group consisting of V, I, L, F, C, A, and T;
- each M12 is, independently, an amino acid selected from the group consisting of S, G, A, N, Q, R, T, K, E, H, D, P, I, F, V, C, Y, L, M, and W;
- each M13 is, independently, an amino acid selected from the group consisting of T, Q, N, S, D, P, F, A, E, G, H, L, C, K, V, R, Y, I, M, and W;
- each M14 is, independently, an amino acid selected from the group consisting of L, F, I, V, M, Y, A, T, Q, N, S, D, K, P, E, R, H, G, and C;
- each M15 is, independently, an amino acid selected from the group consisting of S, P, V, E, T, A, F, L, N, R, G, Q, K, H, D, I, C, Y, M, and W;
- each M16 is, independently, an amino acid selected from the group consisting of T, S, A, E, G, C, R, P, Y, M, V, W, I, F, L, Q, N, D, H, and K;
- each M17 is, independently, an amino acid selected from the group consisting of D, E, Q, T, K, P, F, N, S, G, A, Y, R, and V;
- each M18 is, independently, an amino acid selected from the group consisting of G, S, H, P, R, D, N, A, T, Q, E, C, Y, V, I, L, W, F, K, and M;
- each M19 is, independently, an amino acid selected from the group consisting of T, P, F, S, A, E, G, C, R, Y, M, V, W, I, L, Q, N, D, H, and K;
- each M20 is, independently, an amino acid selected from the group consisting of L, F, I, V, Y, A, T, Q, S, D, M, N, K, P, E, R, H, G, and C;
- each M21 is, independently, an amino acid selected from the group consisting of F, L, W, Y, and P;
- each M22 is, independently, an amino acid selected from the group consisting of P, K, Y, A, T, Q, S, G, D, R, C, V, I, L, and H;
- each M23 is, independently, an amino acid selected from the group consisting of T, P, F, S, A, E, G, C, R, Y, M, V, W, I, L, Q, N, D, H, and K;
- each M24 is, independently, an amino acid selected from the group consisting of S, T, A, N, R, G, E, P, V, F, L, Q, K, H, D, I, C, Y, M, and W;
- each M25 is, independently, an amino acid selected from the group consisting of F, W, Y, and P;
- each M26 is, independently, an amino acid selected from the group consisting of T, P, F, Q, N, S, A, E, G, D, K, Y, C, V, I, L, and H;
- each M27 is, independently, an amino acid selected from the group consisting of D, E, Q, N, S, T, R, K, G, A, Y, P, V, and F;
- each M28 is, independently, an amino acid selected from the group consisting of T, Q, N, S, A, G, C, R, K, P, Y, M, V, I, L, F, E, W, D, and H;
- each M29 is, independently, an amino acid selected from the group consisting of S, T, E, A, P, V, F, L, N, R, G, Q, K, H, D, I, C, Y, M, and W;
- each M30 is, independently, an amino acid selected from the group consisting of D, Q, N, H, K, G, C, and Y;
- each M31 is, independently, an amino acid selected from the group consisting of F, L, W, Y, and P;
- each M32 is, independently, an amino acid selected from the group consisting of S, T, E, A, P, V, F, L, N, R, G, Q, K, H, D, I, C, Y, M, and W;
- each M33 is, independently, an amino acid selected from the group consisting of A, G, S, Q, N, K, D, T, C, Y, E, H, V, W, I, L, F, P, R, and M;
- each M34 is, independently, an amino acid selected from the group consisting of T, A, V, I, P, F, Q, N, S, E, G, D, K, Y, C, L, and H;
- each M35 is, independently, an amino acid selected from the group consisting of G, S, R, N, H, D, P, A, T, Q, E, C, Y, V, I, L, W, F, K, and M;
- each M36 is, independently, an amino acid selected from the group consisting of T, Q, S, A, E, D, K, H, P, Y, V, W, I, F, L, N, G, and C;
- each M37 is, independently, an amino acid selected from the group consisting of I, L, W, V, and M;
- each M38 is, independently, an amino acid selected from the group consisting of A, G, S, Q, N, K, D, C, P, R, Y, E, V, W, T, H, M, and F;
- each M39 is, independently, an amino acid selected from the group consisting of S, T, E, P, V, A, F, L, N, R, G, Q, K, H, D, I, C, Y, M, and W;
- each M40 is, independently, an amino acid selected from the group consisting of T, S, A, D, P, M, Q, E, K, H, Y, V, W, I, F, L, N, G, and C;
- each M41 is, independently, an amino acid selected from the group consisting of L, F, I, V, Y, A, T, Q, S, D, M, N, K, P, E, R, H, G, and C;
- each M42 is, independently, an amino acid selected from the group consisting of P, Y, A, T, Q, S, N, W, G, I, E, D, L, K, and H;
- each M43 is, independently, an amino acid selected from the group consisting of S, E, P, V, T, A, F, L, N, R, G, Q, K, H, D, I, C, Y, M, and W;
- each M44 is, independently, an amino acid selected from the group consisting of N, Q, S, E, D, T, H, K, G, A, P, W, and F;
- each M45 is, independently, an amino acid selected from the group consisting of V, I, L, F, C, A, and T;
- each M46 is, independently, an amino acid selected from the group consisting of A, T, S, N, R, Y, K, D, H, M, L, F, G, Q, C, P, E, V, and W;
- each M47 is, independently, an amino acid selected from the group consisting of I, L, and V;
- each M48 is, independently, an amino acid selected from the group consisting of S, P, V, E, T, A, F, L, N, R, G, Q, K, H, D, I, C, Y, M, and W;
- each M49 is, independently, an amino acid selected from the group consisting of F, V, A, T, Q, N, S, E, G, D, and H;
- each M50 is, independently, an amino acid selected from the group consisting of L, F, I, V, Y, A, T, Q, S, D, M, N, K, P, E, R, H, G, and C;
- each M51 is, independently, an amino acid selected from the group consisting of G, S, R, H, D, P, N, A, T, Q, E, C, Y, V, I, L, W, F, K, and M;
- each M52 is, independently, an amino acid selected from the group consisting of T, N, S, G, C, R, H, A, D, P, M, Q, E, K, Y, V, W, I, F, and L;
- each M53 is, independently, an amino acid selected from the group consisting of I, L, W, V, and M;
- each M54 is, independently, an amino acid selected from the group consisting of P, K, Y, A, T, Q, S, G, D, R, C, V, I, L, and H;
- each M55 is, independently, an amino acid selected from the group consisting of D, E, Q, N, S, K, G, A, Y, P, F, T, R, and V;
- each M56 is, independently, an amino acid selected from the group consisting of L, F, I, V, Y, P, A, T, Q, N, S, G, E, D, K, H, M, C, and R;
- each M57 is, independently, an amino acid selected from the group consisting of S, P, V, E, T, A, F, L, N, R, G, Q, K, H, D, I, C, Y, M, and W;
- each M58 is, independently, an amino acid selected from the group consisting of P, M, V, I, L, and F;
- each M59 is, independently, an amino acid selected from the group consisting of N, Q, S, E, D, T, R, K, G, A, and Y;
- each M60 is, independently, an amino acid selected from the group consisting of G, S, H, P, R, D, N, A, T, Q, E, C, Y, V, I, L, W, F, K, and M;
- each M61 is, independently, an amino acid selected from the group consisting of S, P, V, T, A, R, K, E, H, C, Y, I, F, L, N, Q, G, D, M, and W;
- each M62 is, independently, an amino acid selected from the group consisting of P, K, A, Y, T, Q, S, G, D, R, C, V, I, L, and H;
- each M63 is, independently, an amino acid selected from the group consisting of A, G, S, N, E, K, D, H, M, V, W, I, L, F, T, R, Y, Q, C, and P;
- each M64 is, independently, an amino acid selected from the group consisting of D, E, Q, T, K, P, F, N, S, G, A, Y, R, and V;
- each M65 is, independently, an amino acid selected from the group consisting of L, V, F, I, Y, P, A, T, Q, N, S, G, E, D, K, H, M, C, and R;
- each M66 is, independently, an amino acid selected from the group consisting of S, N, R, T, G, K, E, H, D, A, P, V, C, Y, I, F, L, Q, M, and W;
- each M67 is, independently, an amino acid selected from the group consisting of K, R, H, S, G, N, Q, D, E, T, A, C, P, Y, M, V, W, I, L, and F;
- each M68 is, independently, an amino acid selected from the group consisting of R, K, H, S, G, N, Q, D, E, T, A, C, P, Y, M, V, W, I, L, and F;
- each M69 is, independently, an amino acid selected from the group consisting of S, A, N, Q, R, T, G, K, E, H, D, A, C, P, Y, M, V, W, I, F, and L;
- and
- each M70 is, independently, an amino acid selected from the group consisting of T, Q, N, S, A, E, G, D, C, R, K, H, P, Y, M, V, W, I, F, and L;
- and
- wherein Formula XV is represented as:
- (N1)b-(N2)b-(N3)b-(N4)b-(N5)b-(N6)b-(N7)b-(N8)b-(N9)b-(N10)b-(N11)b- (N12)b-(N13)b-(N14)b-(N15)b-(N16)b-(N17)b-(N18)b-(N19)b-(N20)b-(N21)b-(N22)b-(N23)b-(N24)b-(N25)b-(N26)b-(N27)b-(N28)b-(N29)b-(N30)b-(N31)b-(N32)b-(N33)b-(N34)b-(N35)b-(N36)b-(N37)b-(N38)b-(N39)b-(N40)b-(N41)b-(N42)b-(N43)b-(N44)b-(N45)b-(N46)b-(N47)b-(N48)b-(N49)b-(N50)b-(N51)b-(N52)b-(N53)b-(N54)b-(N55)b-(N56)b-(N57)b-(N58)b-(N59)b-(N60)b-(N61)b-(N62)b-(N63)b-(N64)b-(N65)b-(N66)b-(N67)c-(N68)r-(N69)r-(N70)r-(N71)c (Formula XV);
- wherein:
- each b is, independently, 0, 1, 2, or 3;
- and
- each c is, independently, 1 or 2;
- wherein:
- each N1 is, independently, an amino acid selected from the group consisting of S, N, D, Q, R, T, G, E, H, A, P, M, V, K, Y, W, F, L, I, and C;
- each N2 is, independently, an amino acid selected from the group consisting of P, A, S, Y, V, T, G, I, E, and C;
- each N3 is, independently, an amino acid selected from the group consisting of T, S, G, D, C, A, L, N, R, P, Y, V, W, I, and F;
- each N4 is, independently, an amino acid selected from the group consisting of S, R, E, A, Q, K, N, D, T, G, H, C, P, Y, I, F, L, M, V, and W;
- each N5 is, independently, an amino acid selected from the group consisting of T, Q, N, G, C, M, S, A, E, D, Y, V, I, F, L, and W;
- each N6 is, independently, an amino acid selected from the group consisting of I, V, L, F, W, Y, A, T, S, E, D, and H;
- each N7 is, independently, an amino acid selected from the group consisting of P, V, A, S, N, G, E, L, and K;
- each N8 is, independently, an amino acid selected from the group consisting of A, G, Q, T, S, N, P, R, D, V, K, C, Y, W, I, L, and F;
- each N9 is, independently, an amino acid selected from the group consisting of F, Y, A, T, N, and R;
- each N10 is, independently, an amino acid selected from the group consisting of T, Q, N, R, K, M, S, E, D, H, P, V, W, I, F, and L;
- each N11 is, independently, an amino acid selected from the group consisting of A, G, Q, T, S, N, P, R, D, V, K, C, Y, W, I, L, and F;
- each N12 is, independently, an amino acid selected from the group consisting of S, N, Q, R, T, G, K, E, H, D, A, P, L, M, V, Y, W, F, I, and C;
- each N13 is, independently, an amino acid selected from the group consisting of L, F, I, W, V, M, Y, C, A, T, Q, N, S, G, E, D, and R;
- each N14 is, independently, an amino acid selected from the group consisting of V, I, L, A, T, S, G, R, P, Y, N, H, C, M, F, Q, E, K, and D;
- each N15 is, independently, an amino acid selected from the group consisting of S, N, Q, T, G, K, E, H, D, A, C, P, Y, I, F, L, R, M, V, and W;
- each N16 is, independently, an amino acid selected from the group consisting of T, N, S, A, D, R, P, Y, V, W, I, F, and L;
- each N17 is, independently, an amino acid selected from the group consisting of S, N, Q, R, K, E, D, A, T, G, H, C, P, Y, I, F, L, M, V, and W;
- each N18 is, independently, an amino acid selected from the group consisting of V, A, T, S, G, R, W, I, C, L, F, E, D, K, P, Y, N, H, M, and Q;
- each N19 is, independently, an amino acid selected from the group consisting of T, Q, N, S, A, E, G, D, Y, M, V, I, F, L, and W;
- each N20 is, independently, an amino acid selected from the group consisting of S, Q, R, K, E, A, N, D, T, G, H, C, P, Y, I, F, L, M, V, and W;
- each N21 is, independently, an amino acid selected from the group consisting of V, W, I, C, L, F, A, T, S, E, D, K, G, R, P, Y, N, H, M, and Q;
- each N22 is, independently, an amino acid selected from the group consisting of T, Q, N, S, A, D, C, K, P, Y, M, V, W, I, F, G, E, H, R, and L;
- each N23 is, independently, an amino acid selected from the group consisting of L, F, I, V, P, A, T, Q, S, G, R, K, H, M, Y, and D;
- each N24 is, independently, an amino acid selected from the group consisting of T, Q, S, A, G, P, Y, I, K, H, V, F, L, N, D, C, M, W, E, and R;
- each N25 is, independently, an amino acid selected from the group consisting of S, R, E, A, Q, K, N, D, T, G, H, C, P, Y, I, F, L, M, V, and W;
- each N26 is, independently, an amino acid selected from the group consisting of T, N, D, S, A, R, P, Y, V, W, I, F, and L;
- each N27 is, independently, an amino acid selected from the group consisting of D, N, R, E, Q, S, H, T, K, G, W, I, P, and Y;
- each N28 is, independently, an amino acid selected from the group consisting of V, A, T, S, G, R, W, I, C, L, F, E, D, K, P, Y, N, H, M, and Q;
- each N29 is, independently, an amino acid selected from the group consisting of T, S, A, D, C, L, N, R, P, Y, V, W, I, and F;
- each N30 is, independently, an amino acid selected from the group consisting of P, Y, V, A, T, S, G, I, E, and C;
- each N31 is, independently, an amino acid selected from the group consisting of T, Q, S, A, G, K, H, P, Y, V, I, F, L, N, D, C, M, W, E, and R;
- each N32 is, independently, an amino acid selected from the group consisting of S, R, E, A, Q, K, N, D, T, G, H, C, P, Y, I, F, L, M, V, and W;
- each N33 is, independently, an amino acid selected from the group consisting of E, D, Q, N, S, T, H, R, G, A, P, F, and L;
- each N34 is, independently, an amino acid selected from the group consisting of D, N, R, E, Q, S, H, T, K, G, W, I, P, and Y;
- each N35 is, independently, an amino acid selected from the group consisting of T, Q, S, A, G, P, Y, I, K, H, V, F, L, N, D, C, M, W, E, and R;
- each N36 is, independently, an amino acid selected from the group consisting of G, S, K, A, T, Q, D, C, P, Y, V, W, I, L, and F;
- each N37 is, independently, an amino acid selected from the group consisting of F, Y, A, T, N, and R;
- each N38 is, independently, an amino acid selected from the group consisting of V, A, T, S, G, R, W, I, C, L, F, E, D, K, P, Y, N, H, M and Q;
- each N39 is, independently, an amino acid selected from the group consisting of L, F, I, W, V, M, C, A, T, Q, N, S, G, D, R, K, and H;
- each N40 is, independently, an amino acid selected from the group consisting of P, A, S, Y, V, T, G, I, E, and C;
- each N41 is, independently, an amino acid selected from the group consisting of D, N, R, G, Y, E, Q, S, H, T, K, W, and I;
- each N42 is, independently, an amino acid selected from the group consisting of S, R, E, A, N, T, G, P, V, Q, K, H, D, Y, M, I, F, L, C, and W;
- each N43 is, independently, an amino acid selected from the group consisting of G, S, R, K, A, N, Q, H, E, D, P, W, L, and F;
- each N44 is, independently, an amino acid selected from the group consisting of T, Q, S, A, G, P, Y, I, N, E, D, C, K, H, R, V, L, M, F, and W;
- each N45 is, independently, an amino acid selected from the group consisting of S, T, G, A, V, I, R, E, N, P, Q, K, H, D, Y, M, F, L, C, and W;
- each N46 is, independently, C;
- each N47 is, independently, an amino acid selected from the group consisting of S, N, R, T, G, K, E, H, D, A, P, Y, V, W, I, L, Q, M, F, and C;
- each N48 is, independently, an amino acid selected from the group consisting of G, S, R, K, N, T, Q, H, E, D, P, I, and L;
- each N49 is, independently, an amino acid selected from the group consisting of T, S, G, D, C, A, L, N, R, P, Y, V, W, I, and F;
- each N50 is, independently, an amino acid selected from the group consisting of V, A, T, S, G, I, R, P, Y, L, N, H, C, M, F, Q, E, and K;
- each N51 is, independently, an amino acid selected from the group consisting of A, T, G, S, Q, N, R, Y, E, H, M, V, W, I, L, and F;
- each N52 is, independently, an amino acid selected from the group consisting of D, E, Q, N, S, T, K, A, Y, P, M, W, I, F, and L;
- each N53 is, independently, an amino acid selected from the group consisting of A, T, C, G, S, N, P, R, K, D, H, M, and F;
- each N54 is, independently, an amino acid selected from the group consisting of L, F, I, V, P, A, T, Q, S, G, R, K, H, M, Y, and D;
- each N55 is, independently, an amino acid selected from the group consisting of E, D, N, T, R, K, G, A, and V;
- each N56 is, independently, an amino acid selected from the group consisting of A, G, Q, T, S, N, P, R, D, V, W, K, C, Y, I, L, and F;
- each N57 is, independently, an amino acid selected from the group consisting of Y, C, N, I, F, and L;
- each N58 is, independently, an amino acid selected from the group consisting of S, T, G, H, A, P, Y, V, F, L, N, R, K, E, D, W, I, Q, M, and C;
- each N59 is, independently, an amino acid selected from the group consisting of I, V, and L;
- each N60 is, independently, S each N61 is, independently, an amino acid selected from the group consisting of G, S, R, K, A, N, T, Q, E, D, P, and Y;
- each N62 is, independently, an amino acid selected from the group consisting of I, V, L, F, W, Y, A, T, S, E, D, and H;
- each N63 is, independently, an amino acid selected from the group consisting of T, Q, N, G, C, M, S, A, E, D, Y, V, I, F, L, and W;
- each N64 is, independently, an amino acid selected from the group consisting of S, N, Q, R, G, K, E, D, P, Y, W, F, T, H, A, V, L, I, M, and C;
- each N65 is, independently, an amino acid selected from the group consisting of A, C, G, S, Q, N, R, Y, E, K, D, H, M, V, I, and L;
- each N66 is, independently, an amino acid selected from the group consisting of V, I, A, T, S, G, R, P, Y, L, N, H, C, M, F, Q, E, K, and D;
- each N67 is, independently, an amino acid selected from the group consisting of S, N, Q, R, T, G, K, E, H, D, A, C, P, Y, M, V, W, I, F, and L;
- each N68 is, independently, an amino acid selected from the group consisting of K, R, H, S, G, N, Q, D, E, T, A, C, P, Y, M, V, W, I, L, and F;
- each N69 is, independently, an amino acid selected from the group consisting of K, R, H, S, G, N, Q, D, E, T, A, C, P, Y, M, V, W, I, L, and F;
- each N70 is, independently, an amino acid selected from the group consisting of D, E, Q, N, S, H, T, R, K, G, A, C, Y, P, M, V, W, I, F, and L;
- each N71 is, independently, an amino acid selected from the group consisting of A, T, C, G, S, Q, N, P, R, Y, E, K, D, H, M, V, W, I, L, and F.
378 more elements
A pro-protein signal peptide comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to an amino acid sequence selected from the group consisting of SEQ ID NO. 17, 18, 19, 20, 21, 22, 23, 24, 25, 27, 29, 34, 35, 36, 37, 38, 56, 57, 58, 74, or 75.
A polypeptide comprising a formula of (X1)n(Y1)m-Z1 wherein:
- X1 is a pre-protein signal peptide,
- Y1 is a pro-protein signal peptide, and
- Z1 is a payload protein,
- wherein n is 0-1 and m is 0-1,
- wherein n and m cannot concurrently be 0.
2 more elements
Dependencies are inferred from the claim text.