ALPHA-AMINOALKYLPHOSPHONATE DI(CHLOROPHENYL) ESTERS AS INHIBITORS OF SERINE PROTEASES

被引:16
作者
BODUSZEK, B [1 ]
BROWN, AD [1 ]
POWERS, JC [1 ]
机构
[1] GEORGIA INST TECHNOL, SCH CHEM & BIOCHEM, ATLANTA, GA 30322 USA
来源
JOURNAL OF ENZYME INHIBITION | 1994年 / 8卷 / 03期
关键词
SERINE PROTEASE INHIBITORS; PHOSPHONATE INHIBITORS;
D O I
10.3109/14756369409020197
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
alpha-Aminoalkylphosphonate di(chlorophenyl) esters and (alpha-aminoalkyl)phenylphosphinate phenylesters have been tested as irreversible inhibitors of human neutrophil elastase, porcine pancreatic elastase and chymotrypsin, serine proteases important in biochemical processes. Peptidyl derivatives of diphenyl (alpha-aminoalkyl) phosphonates have previously been shown to be potent and specific inhibitors of serine proteases at low concentrations. Addition of a halogen to the phenoxy group of the inhibitors should make the leaving group more electrophilic, and thus more reactive. Peptide phosphonate inhibitors with chlorine in the meta- or para- positions of the phenoxy ester moiety were synthesized and shown to be potent inhibitors of elastase. Tripeptide phosphonates are more potent inhibitors than dipeptide phosphonates, however, addition of the halogen did not increase the inhibitory potency of these phosphonates with elastase compared to the non-halogenated phosphonates. In the case of chymotrypsin, the halogenated phenoxy esters were more reactive, possibly due to an alternate binding mode. The novel (alpha-aminoalkyl)phenylphosphinate phenylesters were poor inhibitors of serine proteases.
引用
收藏
页码:147 / 158
页数:12
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