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Biomimicry as a basis for drug discovery

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Progress in Drug Research

Part of the book series: Progress in Drug Research ((PDR,volume 51))

Summary

Selected works are discussed which clearly demonstrate that mimicking various aspects of the process by which natural products evolved is becoming a powerful tool in contemporary drug discovery. Natural products are an established and rich source of drugs. The term “natural product” is often used synonymously with “secondary metabolite.” Knowledge of genetics and molecular evolution helps us understand how biosynthesis of many classes of secondary metabolites evolved. One proposed hypothesis is termed “inventive evolution.” It invokes duplication of genes, and mutation of the gene copies, among other genetic events. The modified duplicate genes, per se or in conjunction with other genetic events, may give rise to new enzymes, which, in turn, may generate new products, some of which may be selected for. Steps of the inventive evolution can be mimicked in several ways for purpose of drug discovery. For example, libraries of chemical compounds of any imaginable structure may be produced by combinatorial synthesis. Out of these libraries new active compounds can be selected. In another example, genetic system can be manipulated to produce modified natural products (“unnatural natural products”), from which new drugs can be selected. In some instances, similar natural products turn up in species that are not direct descendants of each other. This is presumably due to a horizontal gene transfer. The mechanism of this inter-species gene transfer can be mimicked in therapeutic gene delivery. Mimicking specifics or principles of chemical evolution including experimental and test-tube evolution also provides leads for new drug discovery.

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Abbreviations

6-dEB:

6-deoxyerythronolide B

PKS:

polyketide synthase

FAS:

fatty acid synthase

ACP:

acyl carrier protein

AT:

acyltransferase

KS:

ketosynthase

KR:

ketoreductase

DH:

dehydrase

ER:

enoylreductase

TE:

thioesterase

EDP:

electron pulse delivery

DMF:

dimethylformamide

PCR:

polymerase chain reaction

SELEX:

systematic evolution of ligands by exponential enrichment

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  1. Department of Chemistry, University of Wisconsin-Parkside, Kenosha, WI, 53141, USA

    Vera M. Kolb

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    Ernst Jucker

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Kolb, V.M. (1998). Biomimicry as a basis for drug discovery. In: Jucker, E. (eds) Progress in Drug Research. Progress in Drug Research, vol 51. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8845-5_5

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