Correlation between the conformation of nucleoside antibiotics and their biological activity

Abstract

AbstractNucleoside antibiotics, which result as a consequence of minor modifications in pyrimidine and purine nucleosides, exhibit a wide variety of antiviral, antibacterial, antitumor, and cancerostatic properties. The conformational properties of a number of these antibiotics have been investigated by using the quantummechanical PCILO method, and the results indicate that the nucleoside antibiotics and their parent nucleosides have very similar conformational preferences. This similarity is strikingly marked in the situations which prevail in an aqueous medium. As a result, these antibiotics easily get incorporated in growing chains of RNA and DNA by mimicking their parent nucleosides and then bring about the inhibition of protein, RNA, or DNA syntheses. The experimental observations corroborate these deductions, and thus a correlation has been obtained between the conformation and the biological activity of nucleoside antibiotics; it is the striking conformational similarity between the nucleoside antibiotics and their parent nucleosides which gives rise to their biological activity. The PCILO investigations carried out on two 3‐deazapurine nucleosides demonstrate that the converse of the above correlation also holds true.