deSolms S J, Deana A A, Giuliani E A, Graham S L, Kohl N E, Mosser S D, Oliff A I, Pompliano D L, Rands E, Scholz T H
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
J Med Chem. 1995 Sep 29;38(20):3967-71. doi: 10.1021/jm00020a010.
A series of pseudodipeptide amides are described that inhibit Ras protein farnesyltransferase (PFTase). These inhibitors are truncated versions of the C-terminal tetrapeptide (CAAX motif) of Ras that serves as the signal sequence for PFTase-catalyzed protein farnesylation. In contrast to CAAX peptidomimetics previously reported, these inhibitors do not have a C-terminal carboxyl moiety, yet they inhibit farnesylation in vitro at < 100 nM. Despite the absence of the X residue in the CAAX motif, which normally directs prenylation specificity, these pseudodipeptides are greater than 100-fold selective for PFTase over type 1 protein geranylgeranyltransferase.
描述了一系列抑制Ras蛋白法尼基转移酶（PFTase）的假二肽酰胺。这些抑制剂是Ras C端四肽（CAAX基序）的截短版本，该四肽充当PFTase催化的蛋白质法尼基化的信号序列。与先前报道的CAAX拟肽不同，这些抑制剂没有C端羧基部分，但它们在体外以小于100 nM的浓度抑制法尼基化。尽管CAAX基序中通常指导异戊二烯化特异性的X残基缺失，但这些假二肽对PFTase的选择性比对1型蛋白质香叶基香叶基转移酶高100倍以上。
