Colchicine photosensitizes covalent tubulin dimerization.
Pure rat brain tubulin can be cross-linked by ultraviolet irradiation of tubulin-colchicine complexes at the high-wavelength maximum of colchicine to form covalent dimers greater than trimers greater than tetramers. With colchicine concentrations approximately 3 x 10(-4) M (mole ratio to tubulin 3-12) and irradiation for 5-10 min at 95-109 mW/cm2, the yield of dimers is 11-17% and of trimers is 4-6% of the total tubulin. The oligomers show polydispersity and anomalously high apparent molecular masses that converge toward expected values in low-density gels. Maximal dimer yields are obtained with MTC and the decreasing photosensitizing potency is MTC greater than colchicine greater than colchicide greater than isocolchicine greater than thiocolchicine. Single-ring troponoids also promote dimerization. Evidence is presented suggesting that the initial, low-affinity, binding step of colchicine and its analogues is sufficient to photosensitize tubulin dimerization.
Wolff
J
J
Laboratory of Biochemical Pharmacology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Hwang
J
J
Sackett
D L
DL
Knipling
L
L
D000818:Animals; D001923:Brain Chemistry; D003078:Colchicine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D046911:Macromolecular Substances; D015394:Molecular Structure; D010777:Photochemistry; D051381:Rats; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays
D046911:Macromolecular Substances; D014404:Tubulin; D003078:Colchicine