Structure-activity relationship of short analogues of antistasin(ATS)and ghilantens(GLS)including different basic amino acids in 109 position

摘要

ATS,a 15kDa anticoagulant protein isolated from salivary glands of the Mexican leech Haementeria officinalis,has been shown to be a potent inhibitor of factor Xa in the blood coagulation cascade.GLS are potent anticoagulant-antimetastatic proteins that are produced in the salivary gland cells of the proboscis leech Haementeria ghilianii,a predatory annelid indigenous to the Amazon basin and surrounding region of South America.The differences between sequences 109 to 116 of rATS and natural GLS are such that in the position 109 Arg residue is replaced by Lys and in the position 115 He residue is replaced by Val.In order to investigate the biological acivity of sequence 109-116 of GLS,the role of hydrophilic amino acids Arg and Lys in 109 position,and the role of basic group in 109 position,on the anticoagulant activity,analogues of ATS and GLS including Arg,Lys and Orn in the N-terminus were synthesized.On the assumption that replacement of COOH function with CONLL would lead to an increase in stability of peptides against enzymatic hydrolysis,its amides were synthesized,too.