Molecular Pharmacology, Vol 8, 751-758, Copyright © 1972 by the American Society for Pharmacology and Experimental Therapeutics

Induced Conformational Changes in Novobiocin

¹ Department of Radiation Biology and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642

The techniques of ultraviolet absorption spectroscopy and circular dichroism have been utilized to demonstrate in the substituted coumarin antibiotic, novobiocin sodium, a conformational change which could be induced by making the solution acidic. By comparing the ultraviolet spectra of novobiocin with those of coumarin and warfarin, a less complex substituted coumarin, the region of interest in the spectrum has been assigned to transitions within the coumarin ring. Upon acidification a large bathochromic shift was observed only for novobiocin, and has been attributed to increased conjugation as a result of an alignment of the benzamido group attached to position 3 of the coumarin skeleton of the drug. Also upon acidification, an inversion in sign of the circular dichroic band has been noted and has been attributed to a movement of the perturbing benzyl group to a negatively rotating quadrant in accordance with the octant rule. The entirely different circular dichroic spectra of the human albumin-novobiocin complex and the bovine albumin-novobiocin complex may be explained in terms of different conformational changes induced in the novobiocin molecule upon being bound to the two proteins.