Cyclic peptides are an emerging class of molecules that prove to be useful in the medicinal field. Previous literature has shown peptides, with a similar amino acid sequence to the collagen binding site on von Willebrand factor (vWF), were able to competitively inhibit the interaction between collagen and vWF. When vWF binds to collagen, it promotes the aggregation of platelets in a blood vessel. If this continues, thrombosis, excessive blood clotting that can result in heart attacks and strokes, can occur. In this study, four similar peptides were synthesized to act as competitive inhibitors to block collagen-vWF binding. A positive “hit” could potentially prevent thrombosis initiation. In this experiment, the peptides HTNpepDap, HTQpepT, HTNpepT, and HTQpepDap were synthesized using novel head-to-tail cyclization techniques in an effort to improve the function and stability of the literature peptides. All four peptides were found to be stable when exposed to various proteases, such as alpha-chymotrypsin and pepsin. An ELISA assay was performed and showed HTNpepDap to be the most competitive with an IC<sub>50</sub> value of 0.48581±0.11506 mM. Current work involves improvements to the HTNpepDap structures by inclusion of more residues from the structure of vWF. Additionally, the literature compounds are being synthesized and studied for a basis of comparison. These compounds represent potential first generation pharamaceuticals to combat thrombosis.

Characterizing novel peptides as anti-thrombosis agents

251st National Meeting (2016)

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