Synthesis and structure-activity relationships of amastatin analogues, inhibitors of aminopeptidase A.
作者:Hiroyasu TOBE、Hajime MORISHIMA、Takaaki AOYAGI、Hamao UMEZAWA、Kunio ISHIKI、Kenji NAKAMURA、Takeo YOSHIOKA、Yasutaka SHIMAUCHI、Taiji INUI
DOI:10.1271/bbb1961.46.1865
日期:——
Stereoisomers and analogues of amastatin, [(2S, 3R)-3-amino-2-hydroxy-5-methylhexanoyl]-L-Val-L-Val-L-Asp, were synthesized and their inhibitory activities towards aminopeptidase A (AP-A) and other arylamidases tested. Among the four stereoisomers of a new amino acid residue in amastatin, the 2S stereoisomers exhibited strong activity. In a series of compounds in which the C-terminal amino acid of amastatin was substituted by other amino acids, the one containing Asp or Glu showed the strongest activity towards AP-A. In a series of compounds in which the second or third residue from the amino terminal of amastatin was substituted by other amino acids, the one containing hydrophobic amino acids showed strong activity. In the study of the relationship of the length of the peptide chain and inhibitory activity, the activity towards AP-A was seen to increase until the length of the peptide reached that of a tetrapeptide.
阿马司他((2S,3R)-3-氨基-2-羟基-5-甲基己酰基-L-缬氨酰-L-缬氨酰-L-天冬氨酸)的立体异构体和类似物被合成,并测试了它们对氨基肽酶A(AP-A)和其他芳基酰胺酶的抑制活性。在阿马司他中一个新的氨基酸残基的四种立体异构体中,2S立体异构体表现出强烈的活性。在一系列将阿马司他C端氨基酸替换为其他氨基酸的化合物中,含有Asp或Glu的化合物对AP-A显示出最强的活性。在一系列将阿马司他从氨基端开始的第二个或第三个残基替换为其他氨基酸的化合物中,含有疏水氨基酸的化合物表现出强烈的活性。在研究肽链长度与抑制活性关系的研究中,随着肽链长度达到四肽水平,对AP-A的活性逐渐增加。