Inhibition of protein synthesis by didemnins: cell potency and SAR.
Basic Information
ID: ALA1133447
Journal: J Med Chem
Title: Inhibition of protein synthesis by didemnins: cell potency and SAR.
Authors: Ahuja D, Geiger A, Ramanjulu JM, Vera MD, SirDeshpande B, Pfizenmayer A, Abazeed M, Krosky DJ, Beidler D, Joullié MM, Toogood PL.
Abstract: Synthetic and naturally occurring didemnins are potent and specific inhibitors of protein synthesis in vitro. Structure-activity analysis indicates a requirement for the intact macrocycle; however, the smaller ring size represented by the didemnin analogue, tamandarin A, is equipotent to didemnin B. Replacement of the N,O-dimethyltyrosine by a N-methylphenylalanine or N-methylleucine residue is also well-tolerated. The rank order for inhibition of protein synthesis in vitro appears to be retained in MCF-7 cells, albeit at much higher potency. This increase in potency is explained for the first time by data indicating that MCF-7 cells can accumulate didemnin B up to 2-3 orders of magnitude compared to the growth medium.
CiteXplore: 11063617
DOI: 10.1021/jm000168v
Patent ID: ┄