Nonconventional amide bond formation catalysis: programming enzyme specificity with substrate mimetics

Brazilian Journal of Medical and Biological Research

F. Bordusa¹ 

[1] ,Max-Planck SocietyHalle/Saale,Germany

关键词: bioorganic chemistry;    enzyme catalysis;    peptide synthesis;    proteases;    substrate mimetics;   

DOI  :  10.1590/S0100-879X2000000500001

来源: SciELO

【 摘 要 】

This article reports on the design and characteristics of substrate mimetics in protease-catalyzed reactions. Firstly, the basis of protease-catalyzed peptide synthesis and the general advantages of substrate mimetics over common acyl donor components are described. The binding behavior of these artificial substrates and the mechanism of catalysis are further discussed on the basis of hydrolysis, acyl transfer, protein-ligand docking, and molecular dynamics studies on the trypsin model. The general validity of the substrate mimetic concept is illustrated by the expansion of this strategy to trypsin-like, glutamic acid-specific, and hydrophobic amino acid-specific proteases. Finally, opportunities for the combination of the substrate mimetic strategy with the chemical solid-phase peptide synthesis and the use of substrate mimetics for non-peptide organic amide synthesis are presented.

【 授权许可】

CC BY   
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