Gene Regulation: The Involvement of Stereochemical Recognition in DNA-Small Molecule Interactions

A broad spectrum of naturally occurring substances and synthetics is known to influence responses in a variety of biological systems. Substances classified as hormones, phytohormones, pheromones, antigens, carcinogens, antibiotics, etc., range widely in structure from exotic steroids to straight chain aliphatics; the functional groups on these small molecules are equally diverse, for example, the presence of esters, amines, alcohols, phosphates, ethers, and others. Despite this chemical diversity, it appears logical to expect some similarity in the mechanisms by which this array of molecular species influences biological processes. The action of some regulatory molecules may involve their initial interactions with proteins which somehow eventually result in gene action. Accordingly, O'Malley and co-workers [1,2] have detailed such a mechanism in the action of steroid hormones with the nonhistone protein components of DNA. Hence, the preferential binding of biologically active molecules in general to chromosomal proteins could result in the exposure and transcription of deoxyribonucleotide sequences with subsequent production of specific receptor proteins. However, the details concerning the origin of a specific protein(s) which recognizes one regulatory molecule from a host of other substances in a cell or the regulation of transcription and translation of genetic information into proteins involved in a given cellular function are not clear. Indeed, inspection of the chemistry of DNA and RNA indicates that while the multiplicity of nucleotide sequences may be responsible for coding the primary structural differences among proteins, the array of specific recognition sites