3′-Azido-3′-deoxythymidine binding to ribonuclease A: Model for drug-protein interaction

✍ Scribed by S. Gaudreau; A. Novetta-Dellen; J. F. Neault; S. Diamantoglou; H. A. Tajmir-Riahi

• Publisher: Wiley (John Wiley & Sons)
• Year: 2003
• Tongue: English
• Weight: 123 KB
• Volume: 72
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.10483

✦ Synopsis

Abstract

Ribonuclease A (RNase A) with several high affinity binding sites is a possible target for many organic and inorganic molecules. 3′‐Azido‐3′‐deoxythymidine (AZT) is the first clinically effective drug for the treatment of human immunodeficiency virus (HIV) infection. The drug interactions with protein and nucleic acids are associated with its mechanism of action in vivo. This study was designed to examine the interaction of AZT with RNase A under physiological conditions. Reaction mixtures of constant protein concentration (2%) and different drug contents (0.0001–0.1 m__M__) are studied by UV‐visible, FTIR, and circular dichroism spectroscopic methods in order to determine the drug binding mode, the drug binding constant, and the effects of drug complexation on the protein and AZT conformations in aqueous solution. The spectroscopic results showed one major binding for the AZT‐RNase complexes with an overall binding constant of 5.29 × 10^5^ M^−1^. An increase in the protein α helicity was observed upon AZT interaction, whereas drug sugar pucker remained in the C2′‐endo/anti conformation in the AZT‐RNase complexes. © 2003 Wiley Periodicals, Inc. Biopolymers (Biospectroscopy), 2003