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Combinatorial Chemistry Print E-mail
Life Sciences - Life Science Article
Written by Dwivedi. A.   
Tuesday, 10 February 2009

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COMBINATORIAL CHEMISTRY: CURRENT APPROACH

Combinatorial chemistry is one of the important new methodologies developed by researchers in the pharmaceutical industry to reduce the time and costs associated with producing effective and competitive new drugs. Through the rapidly evolving technology of combi-chemistry, it is now possible to produce chemical libraries to screen for novel bioactivities. 

COMBINATORIAL CHEMISTRY: CURRENT APPROACH

Dwivedi A.1, Sitoke A. 2, Joshi V. 3, Akhtar A.K. 4* and Chaturvedi M. 5

1, NRI Institute of Pharmaceutical Sciences, Bhopal, M.P.-India

2, SRM College of Pharmacy, Chennai, T.N.-India

3, Shi RNS College of Pharmacy, Gormi, Gwalior, M.P.-India

4, Faculty of Pharmacy, Integral University, Lucknow, U.P-India

5, GRY Institute of Pharmacy, Khargone, M.P.-India

* Corresponding Author

ABSTRACT

Combinatorial chemistry is one of the important new methodologies developed by researchers in the pharmaceutical industry to reduce the time and costs associated with producing effective and competitive new drugs. Through the rapidly evolving technology of combi-chemistry, it is now possible to produce chemical libraries to screen for novel bioactivities.

INTRODUCTION

The main objective of combinatorial chemistry is synthesis of arrays of chemical or biological compounds called libraries.(1) These libraries are screened to identify useful components, such as drug candidates. Synthesis and screening are often treated as separate tasks because they require different conditions, instrumentation, and scientific expertise. Synthesis involves the development of new chemical reactions to produce the compounds, while screening aims to identify the biological effect of these compounds, such as strong binding to proteins and other biomolecular targets (2). With this technique, the migration times of the ligand-receptor pair are significantly longer than the unreactive ligands, and can be interrogated by electrospray mass spectrometry. The mass spectrometric method often provides a direct structural identification of the ligand, either by determination of its molecular weight or by collision-induced dissociation experiments. In the latter case, the molecular ion is selected by a primary mass spectrometer and is driven into a region of high-pressure inert gas for fragmentation. The fragment ions are then used to reconstruct the original molecular structure. This direct approach to screening and assaying has the advantage that the screening is carried out in solution rather than on a solid support, and it avoids steric problems associated with resin-bound molecules. At present the approach seems limited to libraries of about 1000 compounds because of interference from unbound ligands, and limited by sensitivity issues. New strategies using mass spectrometry may eliminate this limit.

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