American Chemical Society
ol035078+_si_001.pdf (159.34 kB)

Concise and Enantioselective Synthesis of Fmoc-Pmp(But)2-OH and Design of Potent Pmp-Containing Grb2-SH2 Domain Antagonists

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journal contribution
posted on 2003-07-19, 00:00 authored by Peng Li, Manchao Zhang, Megan L. Peach, Hongpeng Liu, Dajun Yang, Peter P. Roller
l-Phosphonomethylphenylalanine (l-Pmp) is an important phosphatase-resistant pTyr analogue. A most concise and stereoselective approach to the synthesis of the suitably protected Fmoc-Pmp(But)2-OH was developed in order to incorporate the functionally significant l-Pmp residue into peptides and peptidomimetics efficiently using standard Fmoc protocol. With this key building block, we are able to efficiently synthesize a series of potent Pmp-containing Grb2-SH2 domain antagonists, which can be used as chemotherapeutic leads for the treatment of erbB2-overexpressed breast cancer.