RNA specific molecules: Cytotoxic plant alkaloid palmatine binds strongly to poly(A)

• Published in: Bioorganic & medicinal chemistry letters Vol. 16; no. 9; pp. 2364 - 2368
• Main Authors: Giri, Prabal, Hossain, Maidul, Kumar, Gopinatha Suresh
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.05.2006; Elsevier
• Subjects: Antineoplastic agents; Antineoplastic Agents - chemistry; Berberine Alkaloids - chemistry; Binding; Biological and medical sciences; Circular Dichroism; Drug Evaluation, Preclinical; General aspects; Hydrogen Bonding; ITC; Medical sciences; Molecular Structure; Palmatine; Pharmacology. Drug treatments; Poly A - chemistry; Poly(A); RNA; RNA - chemistry; Spectroscopy; Thermodynamics; Binding; Palmatine; Poly(A); Spectroscopy; ITC; RNA; Antineoplastic agent; Enthalpy; Molecular interaction; Fluorescence spectrometry; Alkaloid; Biological fixation; Circular dichroism spectrometry; Isothermal titration calorimetry; Thermodynamic properties; Spectrophotometry; Ribonucleotide; Polyribonucleotide; Ultraviolet visible spectrometry
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2006.01.124

Palmatine, the plant alkaloid, binds strongly to single stranded (ss) poly(A) by mechanism of partial intercalation, leading to its usefulness in inhibition of gene expression in eukaryotic cells. The cytotoxic plant alkaloid palmatine was found to bind strongly by partial intercalation to single stranded poly(A) structure with binding affinity ( K a) of (8.36 ± 0.26) × 10 5 M −1. The binding of palmatine was characterized to be exothermic and enthalpy driven with one palmatine for every two adenine residues. On the other hand, the binding to the double stranded poly(A) has been found to be significantly weak. This study identifies poly(A) as a potential bio-target for the alkaloid palmatine and its use as a lead compound in antitumor drug screening.