Cystine knot peptides binding to alpha IIb beta 3 integrins and methods of use

摘要

Disclosed are peptides having a cystine knot structural motif and comprising a sequence engineered for specificity against α_IIbβ₃ integrin, found on platelets, and a method of using the same in anti-thrombotic therapies. The present peptides utilize a cystine knot scaffold derived from modified agouti-related protein or agatoxin, An alternate library screening strategy was used to isolate variants of peptides that selectively bound to α_IIbβ₃ integrin or to both α_IIbβ₃ and α_Vβ₃ integrins. Unique consensus sequences were identified within the identified peptides suggesting alternative molecular recognition events that dictate different integrin binding specificities. In addition, the engineered peptides prevented human platelet aggregation in a plasma-based assay and showed high binding affinity for α_IIbβ₃ integrin.