Examination of acylated 4-aminopiperidine-4-carboxylic acid residues in the phosphotyrosyl+1 position of Grb2 SH2 domain-binding tripeptides.
A 4-aminopiperidine-4-carboxylic acid residue was placed in the pTyr+1 position of a Grb2 SH2 domain-binding peptide to form a general platform, which was then acylated with a variety of groups to yield a library of compounds designed to explore potential binding interactions, with protein features lying below the betaD strand. The highest affinities were obtained using phenylethyl carbamate and phenylbutyrylamide functionalities.
Kang
Sang-Uk
SU
Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702-1201, USA.
Choi
Won Jun
WJ
Oishi
Shinya
S
Lee
Kyeong
K
Karki
Rajeshri G
RG
Worthy
Karen M
KM
Bindu
Lakshman K
LK
Nicklaus
Marc C
MC
Fisher
Robert J
RJ
Burke
Terrence R
TR
D000215:Acylation; D001665:Binding Sites; D051380:GRB2 Adaptor Protein / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D009842:Oligopeptides / Q000737:chemistry*; D019000:Phosphotyrosine / Q000737:chemistry*; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D018909:src Homology Domains
D051380:GRB2 Adaptor Protein; D009842:Oligopeptides; D010880:Piperidines; D019000:Phosphotyrosine