SYNTHESIS AND EVALUATION OF 2‐DIAZO‐3,3,3‐TRIFLUOROPROPANOYL DERIVATIVES OF COLCHICINE AND PODOPHYLLOTOXIN AS PHOTOAFFINITY LABELS: REACTIVITY, PHOTOCHEMISTRY, AND TUBULIN BINDING
作者:
Klaus M. Hahn,
Susan Bane Hastie,
Richard J. Sundberg,
期刊:
Photochemistry and Photobiology
(WILEY Available online 1992)
卷期:
Volume 55,
issue 1
页码: 17-27
ISSN:0031-8655
年代: 1992
DOI:10.1111/j.1751-1097.1992.tb04204.x
出版商: Blackwell Publishing Ltd
数据来源: WILEY
摘要:
Abstract—Derivatives of the tubulin polymerization inhibitors colchicine and podophyllotoxin bearing the photoreactive 2‐diazo‐3,3,3‐trifluoropropanoyl (DTFP) group were synthesized for evaluation as potential photoaffinity labels of the tubulin binding site. All labels were assayed for their ability to inhibit tubulin polymerization, andN‐DTFP‐deacetylthiocolchicine was shown to competitively inhibit tubulin‐colchicine binding with aKiof 4–5 μM.The tubulin off‐rate of this analog was similar to that of podophyllotoxin, rather than to the relatively irreversibly bound colchicine. Photochemical solvent insertion reactions of the labels were investigated. Radioactive samples of the two most active labels were prepared and used in initial protein‐labeling experiments, during which the fractional occupancy of tubulin and extent of covalent incorporation were determined. A rearrangement of DTFP amides was encountered which is relevant to the utility of this moiety for use in synthesis of
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