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Enzymatic generation of complex peptides

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Progress in Drug Research / Fortschritte der Arzneimittelforschung / Progrès des recherches pharmaceutiques

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Abstract

Complex peptides have continued to be lead structures in the search of drugs, especially those of microbial sources. In addition, the discovery of active peptides in animal sources including insects and mammals is advancing. As considerable progress has been achieved in the analysis of protein structure, the identification of targets and mechanisms of action is carried out at the molecular levels. For many purposes of structure-function studies the preparation and modification of complex peptides are required, and often chemical strategies are laborious or not available. Efforts have thus been conducted to make use of protein biocatalysts evolved in the producer organisms, exerting their catalytic powers under physiolgical conditions. Such enzymes permit the synthesis of complex metabolites like cyclic peptides in single pot sequential reactions starting from the direct precursor amino acids. In pharmaceutical research recent examples of bioengineering include the in vitro synthesis of immunomod-ulators of the cyclosporin-type and antihelminthics of the ennatin-type, as well as the in vivo synthesis of antifungals of the R106-type. The reasons for biocatalyst-assisted production are amongst others (1) the convenient and rapid access to small amounts of analogs, (2) the option to develop a later bioproduction of a certain analog since natural systems are exploited, and (3) the contribution of knowledge on these systems with a view to developing new systems for the generation of compound libraries.

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  1. Technical University of Berlin, D-10587, Berlin, Germany

    Horst Kleinkauf & Hans von Döhren

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  1. Horst Kleinkauf
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    Ernst Jucker

  2. Basel, Switzerland

    Ernst Jucker

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Kleinkauf, H., von Döhren, H. (1997). Enzymatic generation of complex peptides. In: Jucker, E. (eds) Progress in Drug Research / Fortschritte der Arzneimittelforschung / Progrès des recherches pharmaceutiques. Progress in Drug Research / Fortschritte der Arzneimittelforschung / Progrès des recherches pharmaceutiques, vol 48. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8861-5_2

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  • DOI: https://doi.org/10.1007/978-3-0348-8861-5_2

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