STRUCTURE-ACTIVITY STUDIES OF NONMACROCYCLIC RAPAMYCIN DERIVATIVES

Authors
HOLT DA KONIALIAN AL BRANDT M LEVY MA BOSSARD MJ LUENGO JI NEWMANTARR T BADGER A
Citation
Da. Holt et al., STRUCTURE-ACTIVITY STUDIES OF NONMACROCYCLIC RAPAMYCIN DERIVATIVES, Bioorganic & medicinal chemistry letters, 3(10), 1993, pp. 1977-1980
Citations number
20
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
3
Issue
10
Year of publication
1993
Pages
1977 - 1980
Database
ISI
SICI code
0960-894X(1993)3:10<1977:SSONRD>2.0.ZU;2-O
Abstract
X-ray crystallography suggests the C23-C28 segment of rapamycin may ac t more as an element of the FKBP binding domain than as part of the im munosuppressant effector domain. Selective excision of this region fro m the natural product followed by minor reconstruction of the binding domain resulted in compounds with high affinity for FKBP but no immuno suppressive activity. This, along with data from other secorapamycin a nalogs, suggest the importance of C23-C28 in the orientation of the ef fector domain.