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US 5,849,865 AGranted
Peptides for altering bone resorption, angiogenesis and restenosis
AssigneeLa Jolla Cancer Research Foundation
InventorsSoan Cheng, Ronald Ingram, Daniel Mullen, Juerg F. Tschopp
Life of this patent
Estimating the term…
Abstract
The present invention provides Arg-Gly-Asp peptides that can alter the binding of osteoclasts to a matrix such as bone or can selectively alter integrin receptor binding. The invention also provides methods of using the Arg-Gly-Asp peptides to alter .alpha..sub.v .beta..sub.3 integrin receptor-mediated binding of a cell such as an osteoclast, endothelial cell or smooth muscle cell to a matrix. The invention further provides methods for ameliorating the severity of a pathology characterized, in part, by an undesirable level of bone resorption, angiogenesis or restenosis in a subject.
Claims6
A peptide having the amino acid sequence:
- Mpa-R-G-D-D-V-C-NH.sub.2 (SEQ ID NO:
- 41);
- G-R-G-D-D-V-D-NH.sub.2 (SEQ ID NO:
- 7);
- Ac-C-A-A-R-G-D-S-Tic-C-NH.sub.2 (SEQ ID NO:
- 70);
- G-Pen-A-A-R-G-D-D-V-C-A-NH.sub.2 (SEQ ID NO:
- 63);
- G-Pen-R-A-R-G-D-D-V-C-A (SEQ ID NO:
- 33);
- or
- Mpa-R-G-D-D-(t-BuG)-C-NH.sub.2 (SEQ ID NO:
- 53).
10 more elements
A peptide having the amino acid sequence:
- G-R-G-D-D-(t-BuG)-E-NH.sub.2 (SEQ ID NO:
- 71);
- R-G-D-D-(t-BuG)-(Mamb) (SEQ ID NO:
- 72);
- (Mpa)-R-G-D-(tetA)-(t-BuG)-C-NH.sub.2 (SEQ ID NO:
- 90);
- or
- (Mpa)-R-G-D-D-(t-BuG)-C-F-NH.sub.2 (SEQ ID NO:
- 73).
6 more elements
A peptide having the amino acid sequence:
- R-G-D-D-V-E-NH.sub.2 (SEQ ID NO:
- 3);
- Ac-C-A-A-R-G-D-N-Tic-C-NH.sub.2 (SEQ ID NO:
- 35);
- Ac-Pen-F-A-R-G-D-S-Tic-C-NH.sub.2 (SEQ ID NO:
- 36)
- Ac-C-R-G-D-T-Tic-C-NH.sub.2 (SEQ ID NO:
- 37);
- Ac-C-A-A-R-G-D-T-Tic-C-NH.sub.2 (SEQ ID NO:
- 38);
- Ac-C-R-G-D-S-Tic-Pen-NH.sub.2 (SEQ ID NO:
- 39);
- .beta.Ala-A-A-R-G-D-N-Tic-D-NH.sub.2 (SEQ ID NO:
- 91);
- G-C-E-P-R-G-D-N-Tic-C-A-NH.sub.2 (SEQ ID NO:
- 43);
- G-Pen-A-A-R-G-D-S-P-C-A (SEQ ID NO:
- 44);
- Ac-Pen-F-A-R-G-D-N-Tic-C-NH.sub.2 (SEQ ID NO:
- 45);
- Ac-Pen-(YOMe)-A-R-G-D-N-Tic-C-NH.sub.2 (SEQ ID NO:
- 46);
- Ac-Pen-A-A-R-G-D-N-Tic-C-NH.sub.2 (SEQ ID NO:
- 47);
- Ac-C-R-G-D-S-Tic-C-NH.sub.2 (SEQ ID NO:
- 48);
- Ac-C-R-G-D-N-Tic-Pen-NH.sub.2 (SEQ ID NO:
- 49);
- G-A-A-R-G-D-S-Tic-E-NH.sub.2 (SEQ ID NO:
- 115);
- Ac-Pen-F-A-R-G-D-N-P-C-NH.sub.2 (SEQ ID NO:
- 51);
- Ac-C-E-P-R-G-D-N-Tic-C-NH.sub.2 (SEQ ID NO:
- 55);
- Ac-C-A-A-R-G-D-N-Tic-C-K-NH.sub.2 (SEQ ID NO:
- 52);
- R-G-D-(YOMe)-R-E-NH.sub.2 (SEQ ID NO:
- 67);
- Ac-C-A-A-R-G-D-Y-(Tic)-C-NH.sub.2 (SEQ ID NO:
- 86)
- Ac-C-F-A-R-G-D-T-(Tic)-C-NH.sub.2 (SEQ ID NO:
- 103);
- R-G-D-N-(Tic)-E-NH.sub.2 (SEQ ID NO:
- 105);
- Ac-C-R-G-D-T-(Tca)-C-NH.sub.2 (SEQ ID NO:
- 107);
- T-A-P-G-K-H-P-N-R-C-A-A-R-G-D-N-(Tic)-C (SEQ ID NO:
- 101);
- (Pmp)-A-A-R-G-D-D-N-(Tic)-C-NH.sub.2 (SEQ ID NO:
- 112);
- G-Pen-G-F-R-G-D-E-P-C-NH.sub.2 (SEQ ID NO:
- 62);
- Ac-(Pen)-E-P-R-G-D-D-V-C-NH.sub.2 (SEQ ID NO:
- 114);
- or
- Ac-C-A-A-R-G-D-T-(Tic)-C-NH.sub.2 (SEQ ID NO:
- 92).
54 more elements
A peptide having the amino acid sequence:
- (Mpa)-R-G-D-D-(PgL)-C-NH.sub.2 (SEQ ID NO:
- 116);
- (Mpa)-R-G-D-(Psa)-(t-BuG)-C-NH.sub.2 (SEQ ID NO:
- 117);
- (Mpa)-R-G-D-D-(t-BuG)-C-D-NH.sub.2 (SEQ ID NO:
- 118);
- Ac-C-(N-Me-R)-G-D-T-(Tic)-C-NH.sub.2 (SEQ ID NO:
- 119);
- Ac-F-C-R-G-D-T-(Tic)-C-NH.sub.2 (SEQ ID NO:
- 120);
- (Mpa)-R-G-D-(Msa)-(t-BuG)-C-NH.sub.2 (SEQ ID NO:
- 121);
- (Mpa)-R-G-D-(Cha)-(t-BuG)-C-NH.sub.2 (SEQ ID NO:
- 122);
- (Mpa)-R-G-D-(YOMe)-(t-BuG)-C-NH.sub.2 (SEQ ID NO:
- 123);
- or
- (Mpa)-R-G-D-(Tfsa)-(t-BuG)-C-NH.sub.2 (SEQ ID NO:
- 124).
16 more elements
A peptide having the amino acid sequence:
- Ac-C-R-G-D-N-P-Pen-NH.sub.2 (SEQ ID NO:
- 31);
- G-Pen-A-A-R-G-D-D-T-C-NH.sub.2 (SEQ ID NO:
- 32);
- G-Pen-I-A-R-G-D-D-L-C-A (SEQ ID NO:
- 34);
- Ac-Pen-F-A-R-G-D-D-PgL-C-NH.sub.2 (SEQ ID NO:
- 40);
- R-G-D-N-Tic-E-NH.sub.2 (SEQ ID NO:
- 105);
- Ac-C-E-P-R-G-D-N-Tic-C-NH.sub.2 (SEQ ID NO:
- 55);
- G-Pen-G-H-R-G-D-S-P-C-A (SEQ ID NO:
- 75);
- G-Pmc-R-G-D-C-A (SEQ ID NO:
- 57);
- K-Pen-G-F-R-G-D-E-P-C-R (SEQ ID NO:
- 64);
- K-Pen-G-F-R-G-D-D-P-C-R (SEQ ID NO:
- 65);
- G-Pen-A-A-R-G-D-N-P-C-A (SEQ ID NO:
- 79);
- G-Pen-L-(dF)-R-G-D-T-P-C-A;
- G-Pen-I-F-R-G-D-T-F-C-A (SEQ ID NO:
- 80)
- G-R-G-D-S-P-D-F (SEQ ID NO:
- 10);
- G-Pen-G-E-R-G-D-N-Y-C-A (SEQ ID NO:
- 59);
- F-R-G-D-S-P-E-G (SEQ ID NO:
- 11);
- Ac-Pen-A-A-R-G-D-N-(dhP)-C-NH.sub.2 (SEQ ID NO:
- 81);
- G-Pen-E-A-R-G-D-N-P-C-A (SEQ ID NO:
- 83);
- Ac-Pen-T-A-R-G-D-N-P-C-NH.sub.2 (SEQ ID NO:
- 85);
- R-G-D-S-P-E-NH.sub.2 (SEQ ID NO:
- 13);
- G-R-A-R-G-D-N-P-E-NH.sub.2 (SEQ ID NO:
- 14);
- G-Pen-A-A-R-G-D-V-P-C-A-NH.sub.2 (SEQ ID NO:
- 60);
- Ac-Pen-F-A-R-G-D-S-P-C-NH.sub.2 (SEQ ID NO:
- 87);
- Ac-Pen-(YOMe)-A-R-G-D-N-P-C-NH.sub.2 (SEQ ID NO:
- 88);
- (p-Cl-F)-R-G-D-T-P-D-NH.sub.2 (SEQ ID NO:
- 89)
- R-G-D-T-P-E-NH.sub.2 (SEQ ID NO:
- 15);
- G-Pen-A-A-R-G-D-E-P-C-NH.sub.2 (SEQ ID NO:
- 30);
- G-Pen-E-L-R-G-D-G-W-C-NH.sub.2 (SEQ ID NO:
- 61);
- .beta.-Ala-A-A-R-G-D-N-(Tic)-D-NH.sub.2 (SEQ ID NO:
- 91);
- G-R-G-D-E-P-D-G (SEQ ID NO:
- 16);
- Ac-Pen-A-A-R-G-D-N-(1-Nal)-C-NH.sub.2 (SEQ ID NO:
- 93);
- G-Pen-(dE)-A-R-G-D-S-P-C-NH.sub.2 ;
- Ac-C-A-A-R-G-D-N-(fp)-C-NH.sub.2 (SEQ ID NO:
- 94);
- G-Pen-G-F-R-G-D-S-P-C-NH.sub.2 (SEQ ID NO:
- 95);
- Ac-C-R-G-D-S-(Tic)-C-A-K-NH.sub.2 (SEQ ID NO:
- 50);
- Ac-Pen-F-A-R-G-D-D-V-C-NH.sub.2 (SEQ ID NO:
- 96);
- Ac-Pen-(2-Nal)-A-R-G-D-N-P-C-NH.sub.2 (SEQ ID NO:
- 97);
- Ac-R-G-D-D-V-G-NH.sub.2 (SEQ ID NO:
- 2);
- Ac-C-A-A-R-G-D-N-(7-OMeTic)-C-NH.sub.2 (SEQ ID NO:
- 98);
- A-C-R-G-D-S-P-(Pen)-NH.sub.2 (SEQ ID NO:
- 99);
- Ac-C-A-A-R-G-D-N-(Tic)-C-K-NH.sub.2 (SEQ ID NO:
- 52);
- Ac-Pen-I-(nMeF)-R-G-D-T-F-C-NH.sub.2 (SEQ ID NO:
- 100);
- Ac-Pen-F-A-R-G-D-D-(PgL)-C-NH.sub.2 (SEQ ID NO:
- 102);
- Ac-C-R-G-D-D-V-C-NH.sub.2 (SEQ ID NO:
- 17);
- (Mpa)-R-G-D-D-(Cha)-C-NH.sub.2 (SEQ ID NO:
- 104);
- Ac-C-I-A-R-G-D-D-V-C-NH.sub.2 (SEQ ID NO:
- 18);
- Ac-C-A-A-R-G-D-N-(Tic)-C-A-K-NH.sub.2 (SEQ ID NO:
- 106);
- Ac-C-E-P-R-G-D-D-V-C-NH.sub.2 (SEQ ID NO:
- 19);
- Ac-C-R-G-D-T-(Oic)-C-NH.sub.2 (SEQ ID NO:
- 108);
- Ac-C-E-A-R-G-D-D-V-C-NH.sub.2 (SEQ ID NO:
- 20)
- Ac-(Pen)-E-A-R-G-D-D-V-C-NH.sub.2 (SEQ ID NO:
- 109);
- Ac-(Pen)-A-A-R-G-D-N-(homoP)-C-NH.sub.2 (SEQ ID NO:
- 110);
- R-G-D-S-(Adp)-NH.sub.2 (SEQ ID NO:
- 111);
- Ac-C-E-P-R-G-D-N-(Tic)-C-NH.sub.2 (SEQ ID NO:
- 128);
- or
- A-A-R-G-D-D-V-(Adp)-NH.sub.2 (SEQ ID NO:
- 113).
106 more elements
A peptide having the amino acid sequence:
- (Mpa)-R-G-D-D-(NpG)-C-NH.sub.2 (SEQ ID NO:
- 129);
- Ac-(Pen)-I-G-R-G-D-D-(t-BuG)-C-A (SEQ ID NO:
- 130);
- Ac-C-K-G-D-D-V-C-NH.sub.2 (SEQ ID NO:
- 8);
- Ac-A-C-R-G-D-D-V-C-A-NH.sub.2 (SEQ ID NO:
- 26);
- (Mpa)-R-G-D-D-(t-BuG)-C-A (SEQ ID NO:
- 131);
- Ac-C-A-A-(HomoR)-R-G-D-N-(Tic)-C-NH.sub.2 (SEQ ID NO:
- 132);
- (Mpa)-R-G-D-D-(t-BuG)-C-A-K-NH.sub.2 (SEQ ID NO:
- 133);
- (.beta.Ala)-R-G-D-D-(t-BuG)-D-NH.sub.2 (SEQ ID NO:
- 134);
- (Mpa)-(N-Me-R)-G-D-D-(t-BuG)-C-NH.sub.2 (SEQ ID NO:
- 135);
- (Mpa)-R-G-D-D-V-C-A-K-NH.sub.2 (SEQ ID NO:
- 136);
- Ac-A-C-R-G-D-E-V-C-A-NH.sub.2 (SEQ ID NO:
- 27);
- or
- Ac-(Pen)-(YOMe)-A-R-G-D-T-(Tic)-C-NH.sub.2 (SEQ ID NO:
- 24).
22 more elements
Dependencies are inferred from the claim text.