Project: Research project

Project Details


We shall develop reagents to bind to significant elements of proteins
involved in intracellular transduction via their Src Homology (SH) 2,
and SH3 domains. The proteins involved, Grb2, Lck, Hck, Crk, Abl,
and STAT1 are central to growth factor mediated cell transformation,
the immune response, causation of chronic myologenous leukemia, and
the responses to cytokines. The issues of binding site organization,
design of inhibitors, and delineation of pathways is then likely to be
useful in many specific pathological investigations, including cancer,
diabetes, autoimmune disorders, and response to infections. Reagents
developed from these ligands may have broad investigational, and
potentially therapeutic, application.
The approach used consolidated ligand, in which the natural multiple
binding sites of signal transducing proteins, containing multiple
domains, will be complemented by dual ligands tethered together by
specifically designed linkers. This approach has been shown to be
practical already for Abl SH (32). Small combinatorial peptide
libraries based on structural insights, with topological and liker length
variation will be screened by biochemical means for binding to the
target, and those binding strongly will be subject to further
development, by rational and combinatorial methods.
Effective start/end date1/1/9712/31/01


  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences: $223,282.00
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences


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