The United States of America, As Represented by the Secretary, Department of Health and Human Services

Georgetown University

Ya-Qiu Long

C Richter King

Dajun Yang

Feng-Di Lung

Peter P Roller

A compound of formula:in which L is sulfur, sulfoxide, oxygen or methylene, and a compound of formula:in which (i) aais Adi and aais Glu or (ii) each of aaand aais Adi, L is sulfur, sulfoxide, oxygen or methylene, which compounds (and their conjugates) bind to an SH2 domain in a protein comprising an SH2 domain, are non-phosphorylated, are redox-stable in vivo, are characterized by an ICin vivo of less than about 4.0 &#x3bc;M with respect to the SH2 domain in Grb2, and, upon binding to the SH2 domain of Grb2, have a turn conformation. A conjugate comprising a compound as described above and a carrier agent, a composition comprising (i) a compound or a conjugate as described above and (ii) a carrier, a method of inhibiting binding of an SH2 domain in a protein comprising an SH2 domain to a target protein in an animal, wherein the SH2 domain is contacted with a target protein-binding inhibiting effective amount of a compound or a conjugate as described above, and a method of synthesizing such conjugates.

Redox-stable, non-phosphorylated cyclic peptide inhibitors of SH2 domain binding to target protein, conjugates thereof, compositions and methods of synthesis and use

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Bethesda, MD, United States of America

Ya-Qiu Long