ISSN:
0570-0833
Keywords:
Enzyme catalysis
;
Peptide synthesis
;
Chemistry
;
General Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
In spite of the enormous progress in the synthesis of peptides and proteins using commercial peptide synthesizers and the immense technological possibilities of recombinant DNA technology, a C—N ligase is an indispensable tool for the racemization-free fragment condensation of peptides. Since activation of the C-terminal α-carboxyl group of a peptide segment could cause partial racemization, chemical condensations of peptide fragments are prone to racemization. For the synthesis of the huge number of peptides and proteins, however, nature has only developed the ribosomal peptidyltransferase, which exhibits its full catalytic function independent of the side-chain functions of the amino acids being coupled. However, its function requires coordination with numerous other ribosomal factors. Besides the limited possibilities of using multienzyme complexes of bacterial peptide synthesis systems, the only alternatives to peptidyltransferase are proteases, which, based on their in vivo function as hydrolases, cannot act as ideal ligases. However, by exploiting the intrinsic reversibility of hydrolytic reactions and by adjusting appropriate physicochemical reaction parameters, the protease acitivity can be used in the direction of ligation. Undoubtedly, the course of kinetically controlled, serine and cysteine protease-catalyzed reactions can be more efficiently influenced than the equilibrium-controlled protease-catalyzed synthesis. This article describes the influence of the enzyme specificity on the efficiency of kinetically controlled synthesis and points the way toward a broad exploitation of serine and cysteine proteases for the catalysis of C—N bond formation.
Additional Material:
8 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/anie.199114371
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