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US 2019/0337984 A1Published application
Anti-microbial peptides and method for designing novel anti-microbial peptides
AssigneeRensselaer Polytechnic Institute
InventorsGeorges BELFORT, C. Seth PEARSON, Brian MURRAY, Pankaj Sakharam KARANDE, Jun Ha KWAK, Kathleen A. MCDONOUGH, Zachary Andrew KLOOS
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Abstract
Disclosed herein are novel anti-microbial peptides with inhibitory activity against M. tuberculosis and streptococcus bacteria. Additionally, a method for designing novel anti-microbial peptides is disclosed.
Claims20
A peptide comprising a sequence X1X2X3X4X5X6X7X8X9X10X11X12X13 (SEQ ID NO:
- 6), wherein:
- X1, X2, X4, X6, and X11 are each a hydrophobic amino acid,
- X1 is selected from the group consisting of S, T, N, and Q,
- X5, X12, and X13 are each a cationic amino acid,
- X7, X8, X9, and X10 are selected from the group consisting of a hydrophobic amino acid and a cationic amino acid,
- X7 and X8 cannot both be a hydrophobic amino acid and cannot both be a cationic amino acid,
- X9 and X10 cannot both be a hydrophobic amino acid and cannot both be a cationic amino acid, and one or more of the following:
- (i) X7 and X8 are selected from the group consisting of R and W, wherein X7 and X8 are not the same,
- (ii) X9 and X10 are selected from the group consisting of K and W, wherein X9 and X10 are not the same,
- (iii) X1, X2, X4, X6, and Xii are selected from the group consisting of I, L, and W, and
- (iv) X3 is S or T,
- wherein X5, X12, and X13 are selected from the group consisting K and R.
9 more elements
A method for designing a novel peptide, the method comprising:
- (a) identifying a set of anti-microbial peptides having inhibitory activity against a chosen microbe;
- (b) determining most common length of the anti-microbial peptides within the set;
- (c) determining most common net charge of the anti-microbial peptides within the set;
- (d) determining most common range of hydrophobicity of the anti-microbial peptides within the set;
- (e) determining most common amino acids of the anti-microbial peptides within the set,
- (f) optionally, determining at least one common motif present in the anti-microbial peptides within the set, wherein steps (b) through (e) and the optional step (f) are performed sequentially, non-sequentially, or simultaneously;
- (g) designing an amino acid sequence of the novel peptide by selecting amino acids of the novel peptide using a helical wheel diagram, wherein the novel peptide has the most common length determined in step (b), has the most common net charge determined in step (c), has the most common hydrophobicity determined in step (d), consists of the most common amino acids determined in step (e), and, optionally, has the at least one common motif determined in step (f), wherein the novel peptide has one or more hydrophobic faces and one or more hydrophilic faces as predicted by the helical wheel diagram, wherein at least one hydrophobic face of the one or more hydrophobic faces includes at least one hydrophobic face interruption, wherein the at least one hydrophobic face interruption is positioned within the at least one hydrophobic face and consists of one or two amino acids selected from the group consisting of K, R, H, S, T, N, Q, and combinations thereof;
- (h) employing a software program to generate a three dimensional model of the novel peptide having the amino acid sequence designed in step (g);
- (i) confirming that the three dimensional model of the novel peptide generated in step (h) has an alpha helical structure;
- (j) confirming that the three dimensional model of the novel peptide generated in step (h) has the one or more hydrophobic faces and the one or more hydrophilic faces, wherein steps (i) and (j) are performed sequentially, non-sequentially, or simultaneously;
- (k) repeating steps (g) through (j) if the three dimensional model generated in step (h) does not have an alpha helical structure, does not have the one or more hydrophobic faces, or does not have the one or more hydrophilic faces.
8 more elements
Dependencies are inferred from the claim text.