Book of Abstracts: Albany 2007

category image Albany 2007
Conversation 15
June 19-23 2007

Vinblastine and Its Analogues: A Fluoremetric, NMR and Molecular Modeling Study for DNA Binding

Vinblastine sulfate, a clinical agent for the treatment of leukemia and its simpler structural analogs were studied for the DNA binding by fluorescence, NMR and molecular modeling.

It was demonstrated that the mode of binding is non-specific. It was neither intercalation nor minor groove binding. By these studies it was found that the molecules remain anchored in the minor groove through carboxylic acid terminus and indole ring is stacking in and out between the DNA base pairs on a time scale faster than the fluorescence. The methylene linker between indole ring and carboxylic acid terminus facilitates the better binding mode as compared to short linker with one or no methylene group. The NMR studies of Vinblastine and DNA duplex also suggest that the drug is binding between the GC base pairs as evidenced by their 31P chemical shifts. A complete 1H-NMR assignment of the representative DNA decamer has also been furnished using 2D-NMR techniques.

Prateek Pandya1
G. Suresh Kumar2
Surat Kumar1

1Dept. of Applied Sciences
Faculty of Engineering
Dayalbagh Educational Institute
Dayalbagh, Agra-282 005 India
2Biophysical Chemistry
Indian Institute of Chemical Biology
Kolkata, India

Email: surat_kumar@rediffmail.com