Effect of amino acids near the RGD sequence on binding activities between αIIbβ3 integrin and fibrinogen in the presence of RGD-containing synthetic peptides from elegantin and angustatin

Publication date: Available online 5 September 2017
Source:Peptides
Author(s): Etsuko Oyama, Hidenobu Takahashi, Kazuyuki Ishii
Elegantin and angustatin, which were isolated from the snake venoms of Protobothrops elegans and Dendroaspis angusticeps, markedly inhibit binding between platelet integrins and fibrinogen via the Arg-Gly-Asp (RGD) sequence. Angustatin, which is a three-finger toxin containing the RGD sequence, inhibits platelet aggregation almost ten times more strongly than disintegrin isolated from the venoms of Viperidae and Crotalidae. The RGD sequences of both polypeptides are located at the top of hairpin loops, and the composition of the RGD loop is very important for binding to integrin. We investigated the effects of synthetic RGD loop peptides from angustatin and elegantin on ADP- or collagen-induced platelet aggregation and αIIbβ3-fibrinogen binding. Synthetic angustatin (PRGDMP)-type peptides inhibited platelet aggregation more strongly than elegantin (ARGDDX)-type peptides. In particular, the cyclic angustatin peptide (CPRGDMPC) inhibited ADP- and collagen-induced platelet aggregation at least 10-50 times more strongly than the other peptides. The cyclic angustatin peptide (CPRGDMPC) was also the strongest inhibitor of binding between αIIbβ3 and fibrinogen, the IC50 of this peptide was approximately 2.58μM. Regarding the inhibition of binding between αIIbβ3 and fibrinogen, CPRGDMPC demonstrated a stronger inhibitory and more stable effect in the presence of Mg²⁺ than in the presence of Ca²⁺.



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