CONFORMATION OF THIOCOLCHICINE AND 2 B-RING-MODIFIED ANALOGS BOUND TO TUBULIN STUDIED WITH OPTICAL SPECTROSCOPY
Artikel i vetenskaplig tidskrift, 1991

The interaction of tubulin with thiocolchicine and two thiocolchicine analogues, one lacking the B ring and one with a six-membered B ring, has been studied by using near-UV and CD spectroscopies. Rapid, reversible binding of the latter analogue to tubulin demonstrates the ability of the colchicine binding site to accommodate the phenyltropone system with a more coplanar conformation than is present in free colchicine. There is no evidence, however, that bound thiocolchicine should have a much less twisted conformation than free thiocolchicine. Thiocolchicine and the bicyclic analogue appear to have approximately the same conformation of the phenyltropone system, in both the free and the bound states, suggesting that this conformation has an optimal arrangement of the phenyl and tropone rings for binding to tubulin. In contrast to colchicine and related derivatives, the three thiocolchicine analogues show pronounced near-UV CD bands upon association to tubulin. No simple relation could be found between the sign pattern of the CD components in the near-UV band of the thiocolchicinoid chromophore and its axial chirality.

linear dichroism

magnetic circular-dichroism

derivatives

fluorescence stopped flow

podophyllotoxin

inhibition

kinetics

tropone

crystal-structure

colchicine

binding

Författare

Per Lincoln

Institutionen för fysikalisk kemi

Jerker Nordh

Institutionen för fysikalisk kemi

J Deinum

J. Angstrom

Bengt Nordén

Institutionen för fysikalisk kemi

Biochemistry

0006-2960 (ISSN) 1520-4995 (eISSN)

Vol. 30 1179-1187

Ämneskategorier

Biokemi och molekylärbiologi

DOI

10.1021/bi00219a003