Enzyme Tunnels and Gates As Relevant Targets in Drug Design

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F17%3A00068407" target="_blank" >RIV/00159816:_____/17:00068407 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14310/17:00095541

Výsledek na webu

<a href="https://onlinelibrary.wiley.com/doi/epdf/10.1002/med.21430" target="_blank" >https://onlinelibrary.wiley.com/doi/epdf/10.1002/med.21430</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/med.21430" target="_blank" >10.1002/med.21430</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Enzyme Tunnels and Gates As Relevant Targets in Drug Design

Popis výsledku v původním jazyce

Many enzymes contain tunnels and gates that are essential to their function. Gates reversibly switch between open and closed conformations and thereby control the traffic of small molecules-substrates, products, ions, and solvent molecules-into and out of the enzyme&apos;s structure via molecular tunnels. Many transient tunnels and gates undoubtedly remain to be identified, and their functional roles and utility as potential drug targets have received comparatively little attention. Here, we describe a set of general concepts relating to the structural properties, function, and classification of these interesting structural features. In addition, we highlight the potential of enzyme tunnels and gates as targets for the binding of small molecules. The different types of binding that are possible and the potential pharmacological benefits of such targeting are discussed. Twelve examples of ligands bound to the tunnels and/or gates of clinically relevant enzymes are used to illustrate the different binding modes and to explain some new strategies for drug design. Such strategies could potentially help to overcome some of the problems facing medicinal chemists and lead to the discovery of more effective drugs. (C) 2016 Wiley Periodicals, Inc. Med. Res. Rev., 37, No. 5, 1095-1139, 2017

Název v anglickém jazyce

Enzyme Tunnels and Gates As Relevant Targets in Drug Design

Popis výsledku anglicky

Many enzymes contain tunnels and gates that are essential to their function. Gates reversibly switch between open and closed conformations and thereby control the traffic of small molecules-substrates, products, ions, and solvent molecules-into and out of the enzyme&apos;s structure via molecular tunnels. Many transient tunnels and gates undoubtedly remain to be identified, and their functional roles and utility as potential drug targets have received comparatively little attention. Here, we describe a set of general concepts relating to the structural properties, function, and classification of these interesting structural features. In addition, we highlight the potential of enzyme tunnels and gates as targets for the binding of small molecules. The different types of binding that are possible and the potential pharmacological benefits of such targeting are discussed. Twelve examples of ligands bound to the tunnels and/or gates of clinically relevant enzymes are used to illustrate the different binding modes and to explain some new strategies for drug design. Such strategies could potentially help to overcome some of the problems facing medicinal chemists and lead to the discovery of more effective drugs. (C) 2016 Wiley Periodicals, Inc. Med. Res. Rev., 37, No. 5, 1095-1139, 2017

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

MEDICINAL RESEARCH REVIEWS

ISSN

0198-6325

e-ISSN

—

Svazek periodika

37

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

45

Strana od-do

1095-1139

Kód UT WoS článku

000406877600003

EID výsledku v databázi Scopus

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