Convergent synthesis of potent peptide inhibitors of the Grb2-SH2 domain by palladium catalyzed coupling of a terminal alkyne

J Schoepfer; B Gay; N End; E Muller; G Scheffel; G Caravatti; P Furet

doi:10.1016/s0960-894x(01)00173-1

Convergent synthesis of potent peptide inhibitors of the Grb2-SH2 domain by palladium catalyzed coupling of a terminal alkyne

Bioorg Med Chem Lett. 2001 May 7;11(9):1201-3. doi: 10.1016/s0960-894x(01)00173-1.

Authors

J Schoepfer¹, B Gay, N End, E Muller, G Scheffel, G Caravatti, P Furet

Affiliation

¹ Oncology, Research, NOVARTIS Pharma AG, Basel, Switzerland. joseph.schoepfer@pharma.novartis.com

PMID: 11354377
DOI: 10.1016/s0960-894x(01)00173-1

Abstract

A new strategy was developed to prepare in a very efficient and convergent manner C-terminal modified tripeptides with high affinities for the Grb2-SH2 domain. Using Pd(PPh3)2Cl2 as catalyst, selected naphthyl iodides and triflates were coupled to Ac-Pmp(t-Bu)2-Ac6c-Asn-NH(prop-2-ynyl). The resulting alkyne derivatives were hydrogenated and deprotected to afford potent Grb2-SH2 inhibitors.

MeSH terms

Adaptor Proteins, Signal Transducing*
Catalysis
Crystallography, X-Ray
Enzyme-Linked Immunosorbent Assay
GRB2 Adaptor Protein
Magnetic Resonance Spectroscopy
Models, Molecular
Molecular Conformation
Oligopeptides / chemical synthesis*
Oligopeptides / pharmacology*
Palladium / pharmacology*
Proteins / antagonists & inhibitors
Proteins / genetics*
src Homology Domains / drug effects*

Substances

Adaptor Proteins, Signal Transducing
GRB2 Adaptor Protein
Oligopeptides
Proteins
Palladium