Selection of Peptides That Bind to SRC SH2 Domain

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: N/A
Agency Tracking Number: 21950
Amount: $500,000.00
Phase: Phase II
Program: SBIR
Awards Year: 1994
Solicitation Year: N/A
Solicitation Topic Code: N/A
Solicitation Number: N/A
Small Business Information
26 Landsdowne Street, Cambridge, MA, 02139
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 Mark J. Zoller
 (617) 494-0400
Business Contact
Phone: () -
Research Institution
Mice lacking a functional c-src gene develop osteopetrosis due to a defect in bone resorption by osteoclasts (1). This evidence implicates the role of Src in osteoclast resorption activity. We aim to develop a drug that blocks the action of Src protein kinase as a potential treatment of osteoporosis. To do this, we are targeting a domain of the Src protein kinase termed SH2 (src homology 2). SH2 domains are found on a number of intracellular proteins and function as receptors for tyrosine-phosphorylated polypeptides. Our Phase I goal is to identify peptides that tightly bind to the Src SH2 domain using a technique termed "phage display". A library of pentapeptides is expressed on the surface of M13 phage fused to the gene III protein, a minor M13 coat protein. Each phage displays a single peptide sequence on its surface. The phage library is mixed with immobilized SH2 domain and non-binding phage are removed by washing. Bound phage are eluted and propagated through E. coli to produce a population of phage enriched for sequences that recognize the SH2 domain. Since SH2 domains exhibit a higher affinity for tyrosine-phosphorylated peptides versus nonphosphorylated peptides, we will use several novel approaches to phosphorylate the phage-displayed peptides. The selection cycle is repeated 5-10 times then individual phage are cloned, and the encoded peptides are sequenced. Peptides derived from the selected clones will be synthesized and tested for binding to Src SH2 domain.

* Information listed above is at the time of submission. *

Agency Micro-sites

SBA logo
Department of Agriculture logo
Department of Commerce logo
Department of Defense logo
Department of Education logo
Department of Energy logo
Department of Health and Human Services logo
Department of Homeland Security logo
Department of Transportation logo
Environmental Protection Agency logo
National Aeronautics and Space Administration logo
National Science Foundation logo
US Flag An Official Website of the United States Government