Design, synthesis and structure-activity relationship of a series of fragment analogues of antistasin (ATS) and ghilantens (GLS).
A series of low molecular weight peptide inhibitors of Factor Xa, fragment analogues of ATS and GLS, was designed and synthesized by the SPPS method. The new analogues included different basic amino acids in 109 position. In order to investigate the role of these factors, the newly synthesized peptides were tested for anticoagulant activity. To investigate the change in anticoagulant activity, new peptides were synthesized by replacement of the C-terminal COOH function with CONH2. The biological activity of all compounds was measured in respect to APTT (activated partial thromboplastin time) and IC50 values (the concentrations for doubling APTT clotting times of human plasma) were determined.
Danalev
Dancho L
DL
University of Chemical Technology and Metallurgy, Department of Organic Chemistry, 1756 Sofia, Bulgaria. dantchoboy@abv.bg
Vezenkov
Lybomir T
LT
Grigorova
Boryana
B
D000818:Animals; D000925:Anticoagulants / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D065427:Factor Xa Inhibitors; D006801:Humans; D020128:Inhibitory Concentration 50; D007447:Invertebrate Hormones / Q000138:chemical synthesis* / Q000494:pharmacology; D007865:Leeches; D010314:Partial Thromboplastin Time; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D012471:Salivary Proteins and Peptides; D013329:Structure-Activity Relationship
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D007447:Invertebrate Hormones; D010446:Peptide Fragments; D011480:Protease Inhibitors; D012471:Salivary Proteins and Peptides; C063005:ghilanten; C053155:antistasin