Thomas Jefferson University

Other

Ziwei Huang

Robert Korngold

Zhijia Zhang

Jialun Wang

Renato L Baserga

Bradford A Jameson

Mariana Resnicoff

Swati Choksi

Jiansong Luo

Naiming Zhou

Simei Shan

Dongxiang Liu

Zhixian Lu

Xiaobing Han

Zhaowen Luo

The application concerns a method of identifying compounds that can be used to inhibit undesired human CD4T cell immune responses by identifying compounds that block the interaction of CD4 and MHC, class II, gene products and a method of treatment which comprises administering such an identified compound. The compounds that inhibit undesired human CD4T cell immune responses can be used to treat disease such as multiple sclerosis and to prevent graft rejection and graft versus host disease. More specifically, the application concerns compounds having molecular weights between about 1400 and 400 that mimic three portions of the human CD4 lymphocyte cell surface antigen. The portions are residues 29-35, the C&#x2014;C' loop of the D1 domain; residues 317-323, the C&#x2014;C&#x2032; loop of the D4 domain; and residues 346-353, the CDR3 or FG ridge of the D4 domain of the CD4 molecule. Specific examples of such compounds include cyclic peptides and peptidomimetic.

Mimetics of CD4 that inhibit immune response

The application concerns a method of identifying compounds that can be used to inhibit undesired human CD4T cell immune responses by identifying compounds that block the interaction of CD4 and MHC, class II, gene products and a method of treatment which comprises administering such an identified compound. The compounds that inhibit undesired human CD4T cell immune responses can be used to treat disease such as multiple sclerosis and to prevent graft rejection and graft versus host disease. More specifically, the application concerns compounds having molecular weights between about 1400 and 400 that mimic three portions of the human CD4 lymphocyte cell surface antigen. The portions are residues 29-35, the C-C' loop of the D1 domain; residues 317-323, the C-C&#x2032; loop of the D4 domain; and residues 346-353, the CDR3 or FG ridge of the D4 domain of the CD4 molecule. Specific examples of such compounds include cyclic peptides and peptidomimetic.

CD4-derived peptides that inhibit immune response

Enhancement of peptide cellular uptake

Substituted 4H-chromene derivatives are a new class of compounds that bind to Bcl-2 protein and induce apoptosis in tumor cells. The present invention is directed to an efficient synthetic method for the preparation of these compounds from salicylaldehyde derivatives and alkyl cyanoacetates under solid phase.

Synthesis of 4H-chromene derivatives

Synthetic peptide analogs of chemokines are designed to include the N- and C-terminal portions of the corresponding naturally occurring chemokine. In particular, synthetic peptide analogs of stromal cell-derived factor-1 (SDF-1) are effective in inhibiting HIV-1 entry and infection via the CXC chemokine receptor 4 (CXCR4). Each peptide comprises a peptide segment analog of the SDF-1 N-terminal region joined to a peptide segment analog of the SDF-1 C-terminal region. The peptides are useful for HIV treatment and prophylaxis.

Chemokine-derived synthetic peptides

Small molecule inhibitors of Bcl-2 function are used to induce apoptosis of cells which are subject to Bcl-2, which cells are otherwise subject to Bcl-2 mediated blockage of apoptosis. The compounds are useful for treating cancer, autoimmune disorders and viral infection.

Small molecule inhibitors of BCL-2 proteins

MHC or HLA Class I peptides and compositions thereof are provided for the specific induction of apoptosis of cancer cells in a patient. Methods of treating cancer cells in patients suffering from cancer employing the MHC or HLA Class I peptides of the invention. Also provided are methods of identifying MHC or HLA Class I peptides and variants thereof capable of killing cancerous cells in vivo in a patient suffering from cancer.

MHC peptides and methods of use

Compounds that inhibit CD8 mediated T cell activation and that have a molecular surface that corresponds to the molecular surface of human CD8 at amino acids 38-46 and/or 53-56 and/or 60-67 and pharmaceutical compositions comprising such compounds are disclosed. Methods of inhibiting activation of a human T cell are disclosed. The methods comprise contacting a T cell with a compound that inhibits CD8 mediated T cell activation and that has a molecular surface that corresponds to the molecular surface of human CD8 at amino acids 38-46 and/or 53-56 and/or 60-67. Methods of treating an individual suspected of suffering from or susceptible to graft versus host disease and/or organ rejection are disclosed. The methods comprise administering an effective amount of a compound that inhibits CD8 mediated T cell activation and that has a molecular surface that corresponds to the molecular surface of human CD8 at amino acids 34-46 and/or 53-56 and/or 60-67.

CD8 antagonists

The application concerns a method of identifying compounds that can be used to inhibit undesired human CD4.sup.+ T cell immune responses by identifying compounds that block the interaction of CD4 and class II MHC gene products and a method of treatment which comprises administering such an identified compound. The compounds that inhibit undesired human CD4.sup.+ T cell immune responses can be used to treat disease such as multiple sclerosis and to prevent graft rejection and graft versus host disease. More specifically, the application concerns compounds having molecular weights between about 500 and 150 that bind to the GFCC'C' portion of the D1 domain of human CD4 lymphocyte cell surface antigen.

Use of CD4-binding small molecules to inhibit immune responses

The application concerns a method of identifying compounds that can be used to inhibit undesired human CD4.sup.+ T cell immune responses by identifying compounds that block the interaction of CD4 and MHC, class II, gene products and a method of treatment which comprises administering such an identified compound. The compounds that inhibit undesired human CD4.sup.+ T cell immune responses can be used to treat disease such as multiple sclerosis and to prevent graft rejection and graft versus host disease. More specifically, the application concerns compounds having molecular weights between about 1400 and 400 that mimic three portions of the human CD4 lymphocyte cell surface antigen. The portions are residues 29-35, the C-C' loop of the D1 domain; residues 317-323, the C-C' loop of the D4 domain; and residues 346-353, the CDR3 or FG ridge of the D4 domain of the CD4 molecule. Specific examples of such compounds include cyclic peptides and peptidomimetic.

Growing community of inventors

Champaign, IL, United States of America

Ziwei Huang