Synthesis of RGD analogs incorporating salicylic acid derivatives and study of anticoagulant activity
Abstract
Integrins constitute a large family of heterodimeric cell-surface, transmembrane receptors, which play a major role in cell/cell and cell/matrix adhesive interactions. The Arg-Gly-Asp (RGD) sequence is known to be the integrin recognition site of many extracellular matrix proteins such as fibronectin, osteopontin, collagen, fibrinogen, von Willebrand factor, laminin, etc. On the other hand, it is well known that low doses of aspirin (acetyl salicylic acid) decrease platelet aggregation by causing an inhibitory effect on thromboxane A2 production by platelets. Several antiplatelet strategies have already been developed and are under preclinical or clinical investigation. In the present thesis, the synthesis of linear and cyclic RGD analogs incorporating salicylic acid derivatives is reported. The syntheses of the new analogs were carried out by using classic methods of peptide synthesis in liquid or solid phase. The synthesized compounds were purified by RP-HPLC and lyophilised to give ...
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