tRNA binding with anti-cancer alkaloids–nature of interaction and comparison with DNA–alkaloids adducts

• Published in: Journal of photochemistry and photobiology. B, Biology Vol. 142; pp. 250 - 256
• Main Authors: Tyagi, Gunjan, Agarwal, Shweta, Mehrotra, Ranjana
• Format: Journal Article
• Language: English
• Published: Switzerland Elsevier B.V 01.01.2015
• Subjects: Alkaloids - chemistry; Antineoplastic Agents, Phytogenic - chemistry; DNA - chemistry; DNA Adducts - analysis; Intercalating Agents - chemistry; RNA, Transfer - chemistry; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Vinblastine - chemistry; Vinca; Vincristine - chemistry
• ISSN: 1011-1344; 1873-2682
• DOI: 10.1016/j.jphotobiol.2014.12.009

[Display omitted] •Binding of VCR and VBS with RNA is studied using FTIR and absorption spectroscopy.•Results showed some degree of intercalation of vinca alkaloids into tRNA bases.•Binding with phosphate backbone is indicated with no change in B-DNA conformation.•Both the alkaloids interact with nucleic acid with VCR exerting greater effect. Vincristine and vinblastine are potent anti-proliferative compound whose mechanism of action inside a cell is not well elucidated and the basis of their differential cellular effect is also unknown. This work focuses towards understanding the interaction of vincristine and vinblastine with tRNA using spectroscopic approach. Fourier transform infrared (FTIR) spectroscopy, Fourier transform infrared difference spectroscopy and UV–visible spectroscopy were used to study the binding parameters of tRNA–alkaloids interaction. Both the vinca alkaloids interact with tRNA through external binding with some degree of intercalation into the nitrogenous bases. The alkaloids adduct formation did not alter the A-conformation of the biopolymer and vincristine–tRNA complexes were found to be more stable than that of vinblastine–tRNA complexes. The binding constants (K) estimated for VCR–tRNA and VBS–tRNA complexation are 3×102M−1 and 2.5×102M−1 respectively, which suggests low affinity of alkaloids to tRNA. The study recognizes tRNA binding properties of vital vinca alkaloids and contributes to a better understanding of their mechanism of action and could also help in identifying the reason behind their diverse action in a cell.