Heptapeptide-based modification leading to enhancing the action of MTCA on activated platelets, P-selectin, GPIIb/IIIa.

AIM: The modification of platelet inhibitor to enhance its targeting capacity toward platelets is of clinical importance. Thus, (1R, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-β-carboline-3-carboxylic acid (MTCA), a platelet inhibitor, was modified with Lys(Pro-Ala-Lys)-Arg-Gly-Asp-Val (KKV), platelet targeting peptide, to form MTCA-KKV.

MATERIALS & METHODS: MTCA and MTCA-KKV were synthesized to identify the effect of KKV modification on MTCA and platelets.

RESULTS: Atomic force microscopy imaged MTCA-KKV effectively accumulated on activated platelets. UV spectra showed that MTCA-KKV concentration dependently changed P-selectin and GPIIb/IIIa conformations. For platelet aggregation, the IC50 of MTCA-KKV was approximately 1/10 folds of MTCA.

CONCLUSION: KKV modification led to forming MTCA-KKV that is superior to MTCA in terms of accumulating on activated platelets, targeting P-selectin and GPIIb/IIIa and inhibiting platelet aggregation. MTCA-KKV could be a promising lead for further investigation.