The glycoprotein von Willebrand factor (vWF) helps bind platelets to collagen in areas of vascular damage. This process is necessary for the repair of damaged blood vessels but, left unregulated, it could result in thrombosis, the excessive blood clotting associated with heart attacks and strokes. The goal of this project was to synthesize peptides that mimic a portion of vWF’s collagen-binding site so that they can compete with vWF for the binding of collagen. The peptides, Gly-X-Dap-Trp-Leu-Trp-Glu-Asn, where X was either Gly or Val, were cyclized head-to-tail to increase both their binding capability and resistance to protease degradation. These sequences were based on disulfide cyclized peptides made by Depraetere et al. (<i>Blood</i>, 1998). The polar, unnatural amino acid diaminopropionic acid (Dap) was incorporated into the peptides’ sequence to increase their water solubility and protease resistance. The Dap side chain contains an amine group that allowed the peptide to mimic the free N-terminus of the parent compound to bolster its ability to compete with vWF. The peptides were synthesized utilizing solid-phase methods, purified with reverse phase high performance liquid chromatography, and verified with liquid chromatography mass spectrometry. The properties of the peptides were analyzed using enzyme-linked immunosorbent assays to assess their competitive ability and protease assays for their stability.  These represent potential first generation designs for novel anti-thrombosis therapy.<br/>

Development of stabilized cyclic peptides with potential anti-thrombosis activity

251st National Meeting (2016)

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