The importance of the phenyl-tropolone 'aS' configuration in colchicine's binding to tubulin.
Measuring ellipticities of (+/-)-colchicine and (+/-)-deacetamidocolchicine in the presence of tubulin afforded net positive CD bands with maxima at 340 nm resulting from reduction of the negative ellipticities upon binding of (-) enantiomers to the protein. Results of optical studies together with earlier NMR conformational analysis of these molecules substantiate the hypothesis that colchicinoids bind to tubulin with the phenyl-tropolone moiety in the 'aS' configuration. Natural colchicine which binds to tubulin, therefore, should be referred to as (-)-(aS,7S)-colchicine.
Yeh
H J
HJ
Laboratory of Analytical Chemistry, NIDDK, National Institutes of Health, Bethesda, MD 20892.
Chrzanowska
M
M
Brossi
A
A
D000818:Animals; D002417:Cattle; D002942:Circular Dichroism; D003078:Colchicine / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D014404:Tubulin / Q000378:metabolism*
D014404:Tubulin; D003078:Colchicine