New York University

University of Massachusetts

Molsoft LLC

Xiang-peng Kong

Maxim Totrov

Susan Zolla-Pazner

Timothy J Cardozo

Shan Lu

Joseph Schlessinger

Moosa Mohammadi

Abraham Pinter

Shixia Wang

Ruben Abagyan

Miroslaw K Gorny

Stevan R Hubbard

Alexander Plotnikov

Zhongtao Zhang

The present invention is directed to a recombinant immunogenic polypeptide. The polypeptide includes a loop peptide inserted into an immunogenic scaffold protein. The loop polypeptide has an amino acid sequence which presents the 3074 mAb- or the 2219/2557 mAb-targeted epitope of the HIV gp120 protein and not other known epitopes of the HIV gp120 protein. When used as an immunogen, the polypeptide induces an antibody response which neutralizes heterologous HIV-1 viruses in a pattern similar to that observed for the 3074 mAb- or the 2219/2557 mAb-targeted epitope, respectively. Pharmaceutical compositions containing the immunogenic polypeptide as well as methods of making and using it are also disclosed.

Immunogenic polypeptides comprising a modified loop peptide presenting the HIV-1 GP120 3074 mAb epitope and scaffold proteins containing said peptide

Insertion of HIV-1 V3 loop peptides from the viral glycoprotein gp120 into selected, immunogenic scaffold proteins results in a recombinant polypeptide that is a potent V3 immunogen. V3 immunogens include natural and consensus V3 sequences and cyclic and reverse peptides. Preferred scaffold proteins are Cholera Toxin subunit B and homologues thereof including closely relatedenterotoxins. Such immunogenic polypeptides induce broadly reactive anti-gp120 antibodies specific for V3 epitopes that can neutralize heterologous HIV-1 subtypes and strains. These polypeptide, methods for preparing them, and methods for inducing anti-gp120 (V3-specific) antibody) responses using them are disclosed.

Immunogen comprising the HIV GP120 V3 loop in a conformation that induces broadly neutralizing antibodies

The determination and use of three dimensional structures of receptor protein tyrosine kinases and/or their ligands are described. One particular group of such structures includes three dimensional structures of the extracellular domain of RPTKs. The three dimensional structures of RPTKs can faciliate the design and identification of modulators of RPTK function. Other such structures can include of RPTK ligands, such as stem cell factor or a fragment thereof. Modulators of RPTK function can be used to treat diseases that are mediated by inappropriate RPTK activity.

Crystal of fibroblast growth factor receptor 1 in complex with fibroblast growth factor

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Xiang-peng Kong