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Selection of Peptides That Bind to SRC SH2 Domain

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
21950
Program Year/Program:
1994 / SBIR
Agency Tracking Number:
21950
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
Ariad Pharmaceuticals, Inc.
26 LANDSDOWNE ST Cambridge, MA 02139
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Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 2
Fiscal Year: 1994
Title: Selection of Peptides That Bind to SRC SH2 Domain
Agency: HHS
Contract: N/A
Award Amount: $500,000.00
 

Abstract:

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.

Principal Investigator:

Mark J. Zoller
6174940400

Business Contact:

Small Business Information at Submission:

Ariad Pharmaceuticals, Inc.
26 Landsdowne Street Cambridge, MA 02139

EIN/Tax ID:
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No