Spectral deciphering of the interaction between an intramolecular hydrogen bonded ESIPT drug, 3,5-dichlorosalicylic acid, and a model transport protein.
The present work demonstrates a detailed characterization of the interaction of a bio-active drug molecule 3,5-dichlorosalicyclic acid (3,5DCSA) with a model transport protein Bovine Serum Albumin (BSA). The drug molecule is a potential candidate exhibiting Excited-State Intramolecular Proton Transfer (ESIPT) reaction and the modulation of ESIPT photophysics within the bio-environment of the protein has been exploited spectroscopically to monitor the drug-protein binding interaction. Apart from evaluating the binding constant (K (±10%) = 394 M(-1)) the probable location of the neutral drug molecule within the protein cavity (hydrophobic subdomain IIA) is explored by AutoDock-based blind docking simulation. The rotational relaxation dynamics of the drug within the protein has been interpreted on the lexicon of the two-step and wobbling-in-cone model. Circular dichroism (CD) spectroscopy delineates the effect of drug binding on the protein secondary structure in terms of decrease of α-helical content of BSA with increasing drug concentration. Also the esterase activity of the drug:protein conjugate system is found to be reduced in comparison to the native protein.
Department of Chemistry, University of Calcutta, 92 A. P. C. Road, Calcutta-700009, India. bijan_crgprk@yahoo.co.in
Bijan Kumar
BK
Paul
Debarati
D
Ray
Nikhil
N
Guchhait
D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism*; D002417:Cattle; D002723:Chlorobenzoates; D002942:Circular Dichroism; D005454:Fluorescence Polarization; D008958:Models, Molecular; D011485:Protein Binding; D017433:Protein Structure, Secondary; D012459:Salicylates / Q000737:chemistry / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry
D000890:Anti-Infective Agents; D002723:Chlorobenzoates; D012459:Salicylates; D012710:Serum Albumin, Bovine; C514856:3,5-dichlorosalicylic acid