Arginine Mimetic Structures in Biologically Active Antagonists and Inhibitors
The guanidino residue of arginine in many substrates, inhibitors, and antagonists forms strong ionic interactions with the carboxylate of an aspartic acid moiety, which provides specificity for the basic amino acid residue in the active side. However, a highly basic guanidino moiety incorporated in enzyme inhibitors or receptor antagonists is often associated with low selectivity and poor bioavailability after peroral application. Thus, significant effort is focused on the design and preparation of arginine mimetics that can confer selective inhibition for specific trypsin-like serine proteases and NOS inhibitors as well as integrin receptor antagonists and possess reduced basicity for enhanced oral bioavailability.
This review will describe the survey of arginine mimetics designed to mimic the function of the arginine moiety in numerous peptidomimetic compounds (thrombin inhibitors, factor Xa inhibitors, factor VIIa inhibitors, integrin receptor antagonists, nitric oxide synthase inhibitors), with the aim of obtaining better activity, selectivity and oral bioavailability.
Keywords: Arginine; Arginine analogs; Arginine mimetics; Factor Xa inhibitors; Fibrinogen and vitronectin receptor antagonists; Nitric oxide synthase (NOS) inhibitors; Prodrug; Serine protease inhibitors; TF/FVIIa inhibitors; Thrombin inhibitors
Document Type: Research Article
Affiliations: Faculty of Pharmacy,University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia.
Publication date: 2006-12-01
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