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

Georgetown University

Zhu-jun Yao

Terrence R Burke, Jr

Yang Gao

Dajun Yang

C Richter King

Donald P Bottaro

Jesus V Soriano

Safiye N Atabey

Diane E Breckenridge

The present invention provides phenylalanine derivatives that inhibit SH2 domain binding with a phosphoprotein. These derivatives include compounds of the formula: W&#x2014;Y-(AA)-Z wherein n is 0 to 15; Y is a phenylalanyl radical having a phenyl ring, an amine end, and a carboxyl end, the phenyl ring having one or more substituents, e.g., hydroxyl, carboxyl, formyl, carboxyalkyl, carboxyalkyloxy, dicarboxyalkyl, dicarboxyalkyloxy, dicarboxyhaloalkyl, dicarboxyhaloalkyloxy, and phosphonoalkyl, or phosphonohaloalkyl; W is a moiety attached to the nitrogen of Y and is, e.g., alkylcarbonyl, oxalyl, alkylaminooxalyl, arylaminooxalyl, arylalkylaminooxalyl, or alkoxyoxalyl; AA is an amino acid, the amine end of which is attached to the carboxyl end of Y; and Z is an arylalkylamino or arylheterocyclyl alkylamino; or a salt thereof; with the proviso that W is not arylalkylamino when the phenyl ring of phenylalanyl contains a phosphonoalkyl or phosphonohaloalkyl substituent at a position para to the alkylamido group and the ortho and meta positions are unsubstituted. The present invention further provides precursors suitable for preparing the phenylalanine derivatives and a method for the preparation of the precursors. The present invention further provides conjugates comprising a precursor and a conjugant that are covalently linked. These conjugates have biological and/or pharmacological properties. 

Phenylanine derivatives

Disclosed herein are phenylalanine derivative compounds of the following formulaW&#x2014;Y&#x2014;(AA)&#x2014;Zwherein Y is a phenylalanyl radical, AA is an amino acid, n is an integer of 1 to 15, and substituent variables W and Z are as described herein. The compounds can be used to inhibit SH2 binding with phosphoproteins, and to inhibit proliferation of tumor cells.

Phenylalanine derivatives

Disclosed are methods of inhibiting cell motility, for example, by inhibiting the binding between an intracellular transducer and a receptor protein tyrosine kinase, and more particularly by inhibiting hepatocyte growth factor (HGF) induced cell motility. The present invention also provides a method of inhibiting angiogenesis. The methods of the present invention employ peptides such as phosphotyrosyl mimetics. The present invention further provides methods of preventing and/or treating diseases, disorders, states, or conditions such as cancer, particularly metastatic cancer comprising administering to a mammal of interest one or more peptides of the present invention. Also disclosed are methods of blocking HGF, VEGF, or bFGF-stimulated migration, cell proliferation, and formation of capillary-like structures 

Inhibition of cell motility and angiogenesis by inhibitors of Grb2-SH2-domain

The invention relates to an acylated peptide, namely a compound of formula (I),

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Shanghai, China

Zhu-jun Yao