Circular dichroism studies of type III collagen mimetic peptides with anti- or pro-aggregant activities on human platelets

• Published in: European journal of medicinal chemistry 2009-06, Vol.44 (6), p.2643-2650
• Main Authors: Pêcher, Julien, Pires, Viviane, Djaafri, Ibtissem, Da Nascimento, Sophie, Fauvel-Lafève, Françoise, Legrand, Chantal, Sonnet, Pascal
• Format: Article
• Language: English
• Subjects: Anti-aggregant and pro-aggregant activities; Biological and medical sciences; Blood Platelets - drug effects; Blood. Blood coagulation. Reticuloendothelial system; CD studies; Circular Dichroism - methods; Collagen Type III - chemical synthesis; Collagen Type III - chemistry; Collagen Type III - pharmacology; Drug Evaluation, Preclinical; Humans; Left-handed polyproline II conformation; Life Sciences; Medical sciences; Molecular Mimicry; Oligopeptides - chemical synthesis; Oligopeptides - chemistry; Oligopeptides - pharmacology; Peptide sequence Lys-Hyp-Gly-Glu-Hyp-Ala-Pro-Lys; Pharmacology. Drug treatments; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - chemical synthesis; Platelet Aggregation Inhibitors - chemistry; Platelet Aggregation Inhibitors - pharmacology; Protein Conformation; Protein Structure, Secondary; Structure-Activity Relationship; Thermodynamics; Time Factors; α-Triple-helix peptides
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2008.10.026

We report the synthesis of collagen related peptides containing the peptide sequence Lys-Hyp-Gly-Glu-Hyp-Gly-Pro-Lys. The anti-thrombotic activity effects of different glycine mutations in this sequence were studied in regard with their different adopted conformations. The biological results could be correlated to the glycine propensity to adopt a more stable polyproline II helix conformation. The incorporation of these sequences in “collagen-like” α-triple-helix peptides shows a pro-thrombotic activity compared to a scrambled negative control peptide which possesses no significant activity. [Display omitted]