Rational Approach to Drug-Design

A rational approach to drug design may be viewed from different angles, namely  

Quantum mechanics (or wave mechanics) is composed of certain vital principles derived from fundamental assumptions describing the natural phenomena efifeetively. The properties of protons, neutrons and electrons are adequately explained imder quantum mechanics. The electronie features of the molecules responsible for chemical alterations form the basis of drug molecule phenomena. 

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T. Clark, Quantum chemoinformatics an oxymoron (Part 2), in Rational Approaches to Drug Design, H.-D. Holtje, W. Sippl (Eds.), Prous Science, Barcelona, 2001, pp. 29-40. 

Bohm, H.-J. (2001) Progress in structure-based library design. In Rational approaches to drug design Proceedings of the 13th European Symposium on QSAR, Holtje, H.-D. and Sippl, W. (eds.), Prous Science, Barcelona, pp. 367-371. 

This rational approach to drug design has been adopted in developing a specific inhibitor of the human cellular enzyme, purine nucleoside phosphorylase (PNP). PNP functions in the purine salvage pathway, catalysing the reversible reaction shown below ... 

C13 A. Klamt and F. Eckert, COSMO-RS A novel way from quantum chemistry to free energy, solubility, and general QSAR-descrip-tors for partitioning. In Rational Approaches to Drug Design, Prous Science, Barcelona, 2001. 

Most reversible inhibitors may be further classified as being either competitive, non-competitive or uncompetitive. In competitive inhibition the inhibitor usually binds by a reversible process to the same active site of the enzyme as the substrate. Since the substrate and inhibitor compete for the same active site it follows that they will probably be structurally similar (Figure 7.3). This offers a rational approach to drug design in this area. 

P. Ertl, B. Rohde, P. Selzer, Rational Approaches to Drug Design, Proceedings of the European Symposium on Quantitative Structure-Activity Relationships, 13th, Duesseldorf, Germany, Aug. 27-Sept. 1, 2000. 2001, 451-455. 

An example of the rational approach to drug design is provided by the development of HIV (human immune deficiency virus) protease inhibitors. HIV protease cleaves viral polyproteins - the initial products of translation - into the individual protein components and thus is essential for... 

Ishiki HM, Galembeck SE, do Amaral AT (2001) Rational approaches to drug design. In Proceedings of the 13th European symposium on quantitative structure-activity relationships, Duesseldorf, Germany, 27 Aug-1 Sept, 2000. Prous Science, Barcelona, p 340... 

Zamora, I., Oprea, T. I., Ungell, A. L. Prediction of oral drug permeability, in Rational Approaches to Drug Design, Holtje, H.D., Sippl, W. (eds.), Prous... 

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