Bovine pancreatic ribonuclease A (RNase A) catalyzes the cleavage of P-O5' bonds in RNA on the 3' side of pyrimidine to form cyclic 2', 5'-phosphates. It has several high affinity binding sites that make it possible target for many organic and inorganic molecules. Ligand binding to RNase A can alter protein secondary structure and its catalytic activity. In this review, the effects of several drugs such as AZT (anti-AIDS), cis-Pt (antitumor), aspirin (anti-inflammatory), and vitamin C (antioxidant) on the stability and conformation of RNase A in vitro are compared. The results of UV-visible, FTIR, and CD spectroscopic analysis of RNase complexes with aspirin, AZT, cis-Pt, and vitamin C at physiological conditions are discussed here.

Spectroscopic results showed one major binding for each drug-RNase adduct with K_AZT = 5.29 (±1.6) × 10⁴ M^-1, K_aspirin = 3.57 (±1.4) × 10⁴ M^-1, K_cis-Pt = 5.66 (±1.9) × 10³ M^-1, and K_ascorbate = 3.50 (±1.5) × 10³ M^-1. Major protein unfolding occurred with reduction of α-helix from 29% (free protein) to 20% and increase of β-sheet from 39% (free protein) to 45% in the aspirin-, ascorbate-, and cis-Pt-RNase complexes, while minor increase of α-helix was observed for AZT-RNase adduct.

Key words: Protein; Drug; RNase A; Binding mode; Binding constant; Secondary structure; FTIR; UV-Visible; and CD spectroscopy.