Enzymatic transition state theory and transition state analogue design

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Kinetic isotope effects linked to computational chemistry provide sufficient information to develop geometric and electrostatic potential maps of enzymatic transition states. These are blueprints for the design of transition state analogues. Chemically stable molecules that resemble the transition states provide a wealth of inhibitors with dissociation constants in the picomolar to femtomolar range. Several of these have entered clinical trials, and others are in preclinical development. Determination of KIEs coupled to computational and synthetic chemistry can contribute significantly to the development of a broad spectrum of useful enzymatic inhibitors.

Original languageEnglish (US)
Pages (from-to)28297-28300
Number of pages4
JournalJournal of Biological Chemistry
Volume282
Issue number39
DOIs
StatePublished - Sep 28 2007

Fingerprint

Computational chemistry
Blueprints
Isotopes
Electrostatics
Molecules
Kinetics
Static Electricity
Clinical Trials

ASJC Scopus subject areas

  • Biochemistry

Cite this

Enzymatic transition state theory and transition state analogue design. / Schramm, Vern L.

In: Journal of Biological Chemistry, Vol. 282, No. 39, 28.09.2007, p. 28297-28300.

Research output: Contribution to journalArticle

@article{4c9c25a52f8d4d8f86c016d4bbaa6f00,
title = "Enzymatic transition state theory and transition state analogue design",
abstract = "Kinetic isotope effects linked to computational chemistry provide sufficient information to develop geometric and electrostatic potential maps of enzymatic transition states. These are blueprints for the design of transition state analogues. Chemically stable molecules that resemble the transition states provide a wealth of inhibitors with dissociation constants in the picomolar to femtomolar range. Several of these have entered clinical trials, and others are in preclinical development. Determination of KIEs coupled to computational and synthetic chemistry can contribute significantly to the development of a broad spectrum of useful enzymatic inhibitors.",
author = "Schramm, {Vern L.}",
year = "2007",
month = "9",
day = "28",
doi = "10.1074/jbc.R700018200",
language = "English (US)",
volume = "282",
pages = "28297--28300",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "39",

}

TY - JOUR

T1 - Enzymatic transition state theory and transition state analogue design

AU - Schramm, Vern L.

PY - 2007/9/28

Y1 - 2007/9/28

N2 - Kinetic isotope effects linked to computational chemistry provide sufficient information to develop geometric and electrostatic potential maps of enzymatic transition states. These are blueprints for the design of transition state analogues. Chemically stable molecules that resemble the transition states provide a wealth of inhibitors with dissociation constants in the picomolar to femtomolar range. Several of these have entered clinical trials, and others are in preclinical development. Determination of KIEs coupled to computational and synthetic chemistry can contribute significantly to the development of a broad spectrum of useful enzymatic inhibitors.

AB - Kinetic isotope effects linked to computational chemistry provide sufficient information to develop geometric and electrostatic potential maps of enzymatic transition states. These are blueprints for the design of transition state analogues. Chemically stable molecules that resemble the transition states provide a wealth of inhibitors with dissociation constants in the picomolar to femtomolar range. Several of these have entered clinical trials, and others are in preclinical development. Determination of KIEs coupled to computational and synthetic chemistry can contribute significantly to the development of a broad spectrum of useful enzymatic inhibitors.

UR - http://www.scopus.com/inward/record.url?scp=35348956350&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35348956350&partnerID=8YFLogxK

U2 - 10.1074/jbc.R700018200

DO - 10.1074/jbc.R700018200

M3 - Article

C2 - 17690091

AN - SCOPUS:35348956350

VL - 282

SP - 28297

EP - 28300

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 39

ER -