TY - JOUR
T1 - Colchicine glycorandomization influences cytotoxicity and mechanism of action
AU - Ahmed, Aqeel
AU - Peters, Noël R.
AU - Fitzgerald, Megan K.
AU - Watson, James A.
AU - Hoffmann, F. Michael
AU - Thorson, Jon S.
PY - 2006/11/8
Y1 - 2006/11/8
N2 - The reaction of 70 unprotected, diversely functionalized free reducing sugars with methoxyamine-appended colchicine led to the production of a 58-member glycorandomized library. High-throughput cytotoxicity assays revealed glycosylation to modulate specificity and potency. Library members were also identified which, unlike the parent natural product (a destabilizer), stabilized in vitro tubulin polymerization in a manner similar to taxol. This study highlights a simple extension of neoglycorandomization toward amine-bearing scaffolds and the potential benefit of glycosylating nonglycosylated natural products.
AB - The reaction of 70 unprotected, diversely functionalized free reducing sugars with methoxyamine-appended colchicine led to the production of a 58-member glycorandomized library. High-throughput cytotoxicity assays revealed glycosylation to modulate specificity and potency. Library members were also identified which, unlike the parent natural product (a destabilizer), stabilized in vitro tubulin polymerization in a manner similar to taxol. This study highlights a simple extension of neoglycorandomization toward amine-bearing scaffolds and the potential benefit of glycosylating nonglycosylated natural products.
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U2 - 10.1021/ja064686s
DO - 10.1021/ja064686s
M3 - Article
C2 - 17076473
AN - SCOPUS:33750712392
SN - 0002-7863
VL - 128
SP - 14224
EP - 14225
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 44
ER -