B-RING REGULATION OF COLCHICINE BINDING-KINETICS AND FLUORESCENCE
B-RING REGULATION OF COLCHICINE BINDING-KINETICS AND FLUORESCENCE
复制标题
DOI：
10.1073/pnas.83.7.2052
复制
发表时间：
1986-04-01
影响因子：
11.1
通讯作者：
WOLFF, J
中科院分区：
文献类型：
--
作者：
BHATTACHARYYA, B;HOWARD, R;WOLFF, J
秋水仙碱-微管蛋白相互作用的一些特性，例如结合率、可逆性和药物荧光的促进，与秋水仙碱的 B 环有关。 B 环本身会延迟结合速率，而 C-7 处的取代会导致结合速率进一步降低，这似乎与取代基体积和 N-酰基的存在有关。因此，结合率的降序是2-甲氧基-5-(2'',3'',4''-三甲氧基苯基)托酮>去乙酰氨基秋水仙碱>去乙酰胆水仙碱。秋水酰胺>秋水仙碱>N-苯甲酰脱乙酰秋水仙碱等。这种结合的明显不可逆性似乎与N-酰基的存在更密切相关，而不是与C-7处的大量取代基相关。 C-7 处的取代也会影响托酚酮荧光团。因此，胺（脱乙酰胆水仙碱、秋水仙胺或 N-甲基秋水仙胺）在微管蛋白存在下发出的荧光很弱，而用酰基取代氨基则增强了荧光。 C-7 处 N-酰基的存在对于增强荧光至关重要。我们得出的结论是，除了分子的 A 环和 C 环部分之外，秋水仙碱的 B 环是微管蛋白上结合位点识别的第三个决定簇。
Several properties of the colchicine-tubulin interaction such as association rate, reversibility, and the promotion of drug fluorescence have been related to the B ring of colchicine. The B ring itself retards the binding rate, and substitution at C-7 leads to further binding rate decreases that appear to be related to both substituent bulk and the presence of a N-acyl group. Thus, the decreasing order of binding rates is 2-methoxy-5-(2'',3'',4''-trimethoxyphenyl)tropone > deacetamidocolchicine > deacetylcholchicine .gtoreq. colcemid > colchicine > N-benzoyldeacetylcolchicine, etc. The apparent irreversibility of the binding seems more closely related to the presence of an N-ayl group rather than the bulk of the substituent at C-7. Substitution at C-7 also affects the tropolone fluorophore. Thus, amines (deacetylcholchicine, colcemid, or N-methylcolcemid) fluoresce poorly in the presence of tubulin, whereas substitution of the amino group with an acyl group enhances fluorescence. The presence of an N-acyl group at C-7 is essential for enhanced fluorescence. We conclude that, in addition to A- and the C-ring portion of the molecule, the B ring of colchicine is a third determinant recognized by the binding site on tubulin.