Synthesis and structure–activity relationship of new analogues of antistasin

Abstract

Intensive investigation connected with the development of new anticoagulant agents for the treatment of cardiovascular diseases was carried out. Direct and specific inhibition of thrombin and Factor Xa-like serine proteases in the coagulation cascade has been the focus of many efforts to design novel anticoagulants over the past decade. This work reports the synthesis and biological activity of new anticoagulant peptide analogues of natural isoforms 2 and 3 of antistasin. In addition they include different tripeptide sequences in their molecules, which are highly active inhibitors of different serine proteases such as plasmin, trypsin, thrombin and Factor Xa.

Medicinal leech therapy—an overall perspective

“… 33 Researchers claim that antistasin has both anticoagulant and anti-inflammatory effects, but current studies have often focused on the anticoagulant activity, which seems to be the predominant mechanism of action. 34 The Ghilantens were also found in secretions of Haementeria ghilianii (Amazonian Leech) and they show high structural homology with antistasin. There are only few data about their anticoagulant effects, and other possible functions are controversial due to lack of additional studies.…”

Ribozymomimetic Chemical Synthesis of Peptide Bond Using Phosphorous Acid/Oxirane Mediators

“…They are quite expensive and often have low effectiveness due to bond formation with the target. 16,17 They also activate some secondary reactions during the process of the desired bond formation, such as the dehydration of the CONH 2 function of Gln and Asn caused by DCC. 18 Moreover, dicyclohexyl urea, obtained as a secondary product during the reaction of interbiomonomeric bond synthesis, is difficult or in many cases impossible to remove from the final product.…”

Synthetic and Natural Peptides as Antithrombotic Agents—A View on the Current Development

“…Brancamp et al published in 1991 their investigations on ghilanten-related inhibitors (14). In a series of publications Danalev et al (28,29,30,31,32,33,45,87) and naydenova et al (65,66,67) describe the synthesis of fragment analogues of the antistasin, ghilantens and TAP by studying the role of the basic and D-amino acids at different positions in the molecule for the anticoagulant activity of the compounds. they also synthesise a series of hybrid structures between the isoforms of the antistasin, ghilantens and shortened fragments of tAP realising the above mentioned tripeptide active groups aiming to increase the fragments' activity.…”