Peptide-Bassed Inhibitors of Neu Tyrosine Kinase
Abstract
This project focuses on the product of the Her2/Neu oncogene, a receptor tyrosine kinase (Neu) that is amplified in 25-30% of human primary breast tumors. The goal of this project is to characterize the substrate specificity of Neu using peptide libraries. This report covers the second year of the project. We have isolated Neu from Sf9 cells using a baculovirus expression vector. We have isolated five novel sequences from peptide libraries that are phosphorylated by Neu, and determined the kinetic parameters for phosphorylation using individually-synthesized peptides. One of the sequences, AAEEIYAARRG, is the best synthetic peptide substrate reported to date for Neu. We synthesized potential peptide-based inhibitors of Neu by replacing the tyrosine in this peptide and another sequence with p-carboxy-Phe. The inhibitory potency of this first generation of inhibitors toward Neu was somewhat low. Thus, we plan to test additional inhibitors before proceeding to the final stage of the project, namely examining in vivo inhibition of Neu.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1999
- Accession Number
- ADA375133
Entities
People
- Tod Miller
Organizations
- State University of New York