Unmasking the True Identity of Rapamycin's Minor Conformer.
J Nat Prod
; 86(7): 1862-1869, 2023 07 28.
Article
in En
| MEDLINE
| ID: mdl-37432113
ABSTRACT
Rapamycin, a well-known macrocyclic natural product with myriad biological activities, has been the subject of intense study since its first isolation and characterization over five decades ago. Rapamycin has been found to adopt a single conformation in the solid state (both when protein bound and uncomplexed) and exists as a mixture of two conformations in solution. Early work established that the major conformer in solution is the trans amide isomer but left the minor conformer mostly uncharacterized. Since that time, it has been widely accepted that the minor conformer of rapamycin is the cis amide, based solely on analogy to FK-506, another potent immunosuppressive compound with some shared key structural elements. To address this long-standing and unresolved question, the solution structure of the minor conformer of rapamycin was investigated using a combination of NMR techniques and computational methods and determined to be a trans amide species with rotation about the ester linkage.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sirolimus
/
Amides
Language:
En
Journal:
J Nat Prod
Year:
2023
Document type:
Article
Affiliation country: