Isothermal titration calorimetry: application to structure-based drug design

Authors
Citation
Je. Ladbury, Isothermal titration calorimetry: application to structure-based drug design, THERMOC ACT, 380(2), 2001, pp. 209-215
Citations number
33
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Spectroscopy /Instrumentation/Analytical Sciences
Journal title
THERMOCHIMICA ACTA
ISSN journal
0040-6031 → ACNP
Volume
380
Issue
2
Year of publication
2001
Pages
209 - 215
Database
ISI
SICI code
0040-6031(200112)380:2<209:ITCATS>2.0.ZU;2-R
Abstract
The road to market for drug compounds is a treacherous one, generally invol ving a huge temporal and financial investment. The role of structure-based drug design or lead optimisation ranges wildly in importance in different p harmaceutical companies. The adoption of these aids to provide routes to hi gh affinity ligands has not received widespread acceptance. This is based o n a number of factors, from the perceived failings of such methods, to the belief that rapid screening of compound libraries alone is the most effecti ve way to discover drugs. The panacea of being able to take a computer generated representation of th e structure of a target site of a given biomolecule and rationally design a n high affinity inhibiting compound has proved seemingly unreachable for th ree major reasons: (1) current capabilities in computing; (2) the requireme nt for atomic resolution structural detail; and (3) determination of how st ructural features can be related to the thermodynamics of interactions. It is the last of these points that this review seeks to address. In particula r the use of isothermal titration calorimetry is discussed in the light of the accumulation of accurate thermodynamic data and examples are given wher e this has been applied to understand the structural aspects of formation o f drug-biomolecular complexes. (C) 2001 Elsevier Science B.V. All rights re served.