The alpha IIb beta 3 (α_IIbβ₃) integrin plays an important role in platelet aggregation and thrombosis. The α_IIbβ₃ integrin is known to recognize the Arg-Gly-Asp (RGD) sequence found in extracellular matrix proteins. Small molecule peptide sequences designed with the RGD sequence can mimic and competitively inhibit this interaction. Earlier work suggests that incorporation of the Trp-Pro-Asp (WPD) sequence on the carboxy terminus of the RGD sequence increases the binding potency of the peptide (Scarborough, et al., 1993). Moreover, incorporation of D-phenylalanine in the carboxy terminus of the RGD sequence makes it a selective antagonist for α_Vβ₃ integrin (Dechantsreiter, et al.,1999). In the current study, we have extended this approach to α_IIbβ₃ integrin binding peptides.

Cyclic peptides, cyclo[-RGDWPD-] and cyclo[-RGDf-], were synthesized using standard Fmoc strategies and were extended into bioconjugates with PEG tether and hydrophobic anchors. The bioconjugates were incorporated into targeted submicron-sized bubbles using 5% (w:w) targeted ligands relative to the lipid composition for bubble formation. Cyclic peptides are currently being assessed for binding efficiency using bovine platelet adhesion and cell-based human melanoma assays while targeted bubbles are being evaluated for attachment to fresh clots.