Small molecules discovery in the post-genome era can be considered as the intersection of the genome and the chemical space. This new approach, which can be called 'Chemical Genetics', aims to provide tools to discover new drugs at the interface between genome and chemical world.
Most of the known drugs are still small molecules, despite the development of biotechnology products as drugs. Small molecules discovery in the post-genome era can be considered as the intersection of the genome and the chemical space. This new approach, which can be called 'Chemical Genetics', aims to provide tools to discover new drugs at the interface between genome and chemical world. This can be considered as the future perspective of drug discovery chemistry.
Most of known drugs discovered to date achieve their activity through interactions with a limited number of proteins. But chemists have identified around 20 million molecules, either synthetic or from natural origin. These molecules cover a large panel of properties, among which the ones which make useful drugs.
We may expect the discovery of a few thousands of new proteins of therapeutic relevance, while the theoretical number of small molecules imagined can be high. It indicates, though the number of genes is limited and defined, the chemical space has no boundaries.
The work of the chemist should be focused on extending the chemical diversity to compounds to be screened for their ability to modulate the functions of new proteins. Two methods may be considered- Synthesis of compound libraries through combinatorial chemistry techniques and the use of natural substances.
Researchers must try to find out answers for the questions that arise-
*Natural substances originate from a wide variety of living organisms: are some better than others? What about the synthesis of natural products and analogues?
*How to proceed with the screening? What about cellular versus molecular screening?
*Is it the role of academia laboratories to carry out high throughput screening, or is it the domain of industrial, teams?
(The author is with Laboratoire de Biochimie, France.) (Extracted from the abstract of plenary lecture delivered by ProfessorNicole J Moreau in an Indo-US conference on 'New Bioactive Molecules in Pharmaceutical Research- Contribution of Natural Products' at IICT, Hyderabad during November 13-14, 2006 )