From natural to synthetic multisite thrombin inhibitors.

Abstract:

:A large number of potent and selective therapeutic agents, useful for the treatment of several diseases, have been isolated from natural sources. For example, the most active thrombin inhibitors are those secreted by the salivary glands of leeches. One peculiar feature of these agents is the lack of any significant inhibitory cross-reaction with other serine proteinases. Hence, the knowledge of the exact mechanism of action of these molecules provides the basis for the development of new and efficient synthetic drugs. For this reason, many studies have been undertaken on the structure-activity relationships of natural thrombin inhibitors, and a large amount of detailed information has been obtained by the crystal structures of these inhibitors when complexed with thrombin. In this paper, we review natural and synthetic multisite thrombin inhibitors, whose structural aspects have been determined in detail. We also report here the approach used by us to develop a new class of synthetic, multisite directed thrombin inhibitors, named hirunorms, designed to mimic the distinctive binding mode of hirudin.

journal_name

Biopolymers

journal_title

Biopolymers

authors

Lombardi A,De Simone G,Galdiero S,Staiano N,Nastri F,Pavone V

doi

10.1002/(SICI)1097-0282(1999)51:1<19::AID-BIP4>3.0

subject

Has Abstract

pub_date

1999-01-01 00:00:00

pages

19-39

issue

1

eissn

0006-3525

issn

1097-0282

pii

10.1002/(SICI)1097-0282(1999)51:1<19::AID-BIP4>3.0

journal_volume

51

pub_type

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