Study of Small Ligands Which Bind Specifically to Breast Cancer Cells
Abstract
Our lab uses phage displayed random peptide library (RPL) technology to identify small ligands to breast cancer targets, particularly ErbB2. Small ligands can be coupled to cytotoxic agents and used to mediate the specific destruction of tumor cells. Proof of concept for our project is found in exciting recent reports which describe the identification of tumor-homing peptides which, when conjugated to doxorubucin, effect tumor eradication RPL screening and analysis of binding clones is routine in our lab. We have also developed a novel colony screening assay that greatly increases the number of clones which can be assessed for target binding and an ErbB2 dimerization assay that can be used to detect peptides which inhibit dimerization. We have identified binders to several different targets relevant to breast cancer therapy, including a peptide which inhibits the association of Grb2 and ErbB2 in cell lysates and is being further developed as a potential cancer therapeutic. We have purified ErbB2, used it as a target for RPL screening, and have identified several strong consensus amino acid sequences. The consensus sequences are valuable since higher affinity binders can often be identified from libraries biased for these sequences. A large panel of libraries which present a vast number of peptides presented in a variety of structural contexts is also likely to yield a higher affinity binder to any given target and is presently being constructed.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 1999
- Accession Number
- ADB250311
Entities
People
- David N Krag
Organizations
- University of Vermont