Synthesis of salicyl-peptides and their effect on human platelet aggregationin vitro

Abstract

Summary.A series of leucine dipeptide amides containing at their N-terminal amino group the salicyl-residue [(o)-RO-C<,H4-CO-, where R=H or CH3CO] have been synthesized by conventional solution techniques and tested for their inhibitory activity on human platelet aggregation in vitro induced by collagen, ADP or adrenaline. The salicyl-peptide (o)-HO-C6H4-CO-LeuAsp(OBzl)-NH2 was found to exert strong inhibitory activity on platelet aggregation induced by collagen with an ICs0 value 4.5raM. The corresponding dipetide H2N-Leu-Asp(OBzl)-NH 2 was also examined and was found to be less active, indicating that the presence of the lipophilic fi-benzyl ester group in combination with the salicyl group enhance the inhibitory activity. All the other salicyl-peptides examined either didn't show any inhibitory or aggregatory activity or a slight inhibition at the concentration of 9-10 raM.

Peptide Chemistry's Contribution to the Treatment of the Majority of Serious Illnesses: Peptide Antitumors.

“…They synthesized and developed. George Stavropoulos, et al, [116], stated that the property of peptides containing the sequence Arg-Gly-Asp (RGD) to inhibit platelet aggregation and thrombus formation in vitro has led to research for small peptides or mimtics to be used as antithrombotic drugs. They synthesized a series of salicyl-peptide amides and tested for their inhibitory activity.…”

N-Salicyl-AAn-picolamide Foldameric Peptides Exhibit Quorum Sensing Inhibition of Pseudomonas aeruginosa (PA14)

“…Salicylamide is also considered as a potential scaffold for designing therapeutic peptide drugs by altering the peptide structure and conformation. , Deng has synthesized novel salicylamide derivatives which show selective Ache inhibition, antioxidant features, Ab-aggregation, anti-neuroinflammation, and BBB permeability, a potential drug of Alzheimer’s disease . The N -salicylic-dipeptides inhibit human platelet aggregation, which is induced by collagen, ADP, and adrenaline . However, RGD analogues containing salicylic acid derivatives show antiplatelet activities .…”

“… 6 The N -salicylic-dipeptides inhibit human platelet aggregation, which is induced by collagen, ADP, and adrenaline. 7 However, RGD analogues containing salicylic acid derivatives show antiplatelet activities. 8 De Grado has used salicylic acid for novel self-assembling foldamers that inhibit heparin–protein interactions.…”