Yissum Research Development Company of the Hebrew University of Jerusalem Ltd.

Peptor Limited

University of Michigan

Rhone-Poulenc Rorer Pharmaceuticals Inc.

Other

Technische Universitaet Muenchen

Develogen Israel Ltd.

Technische Universitat Munchen

Chaim Gilon

Alexander Levitzki

Alon Seri-Levy

Doron Eren

Amnon Hoffman

Irina Zeltser

Dan Muller

Aviv Gazit

Gal Bitan

Alfred P Spada

Paul E Persons

Joseph Holoshitz

Song Ling

Michael Chorev

Vered Hornik

Xiujun Pi

Denise De Almeida

Berta Levavi-Sivan

Adi Klinger

Hadas Reuveni

Gabriel Nussbaum

Gary Gellerman

Assaf Friedler

Abraham Loyter

Florian Rechenmacher

Moshe Bentolila

Horst Otto Kessler

Michael Weinmuller

Joseph Fanous

Zvi Zelinger

Gerardo Byk

Gal Gitan

Amnon Wolf

Johnny Naoum

Michael Weinmueller

The present invention provides N-methylated cyclic hexapeptides comprising RGD and at least one alanine residue. The present invention further provides prodrugs comprising the cyclic hexapeptides. Pharmaceutical compositions comprising said cyclic hexapeptides are also disclosed as well as methods of their production and use in treating integrin related conditions and diseases.

N-methylated cyclic peptides and their prodrugs

The present disclosure relates to solid phase synthesis of organic molecules and particularly to highly efficient methods for synthesizing polymers, such as peptides, nucleotides or saccharides, employing solid phase synthesis.

High shear solid phase synthesis

The present invention provides prodrugs of somatostatin peptide and peptide analogs that are tissue permeable and oral bioavailable and enable activity of the somatostatin analog at the circulation or target tissue after cleavage of charge-masking lipophilic moieties. Pharmaceutical compositions comprising these prodrugs and their use in therapy and diagnosis are also provided.

Somatostatin prodrugs

Peptide-based neurokinin antagonists of fish reproduction are disclosed. Compositions comprising antagonists of fish neurokinin and methods of inhibiting or delaying puberty, fish maturation or reproduction processes using these compounds are also provided.

Antagonists of fish reproduction

Provided are backbone cyclized peptides that interfere with signaling of the intracellular adaptor protein MyD88. Pharmaceutical compositions including these backbone cyclized peptides as well as their use in treatment of multiple sclerosis (MS) and other diseases associated with MyD88 signaling are also disclosed.

Backbone cyclized inhibitory peptides of myeloid differentiation factor 88 (MyD88)

Provided are Peptide-based neurokinin antagonists of fish reproduction. Compositions including antagonists of fish neurokinin and methods of inhibiting or delaying puberty, fish maturation or reproduction processes using these compounds are also provided.

Antagonists of neurokinin B in fish reproduction

The present invention relates to methods and compositions for treating disease related to disorders of bone remodeling. In particular, the present invention relates to compositions and methods for treating rheumatoid arthritis.

Methods and compositions for the treatment of bone remodeling disorders

The present invention provides compositions and methods for inducing an immune response in a subject. In particular, the present invention provides compositions comprising immunostimulatory ligands (ISL) and methods of inducing an immune response in a subject therewith. Compositions and methods of the present invention find use in, among other things, clinical (e.g. therapeutic and preventative medicine (e.g., vaccination)) and research applications.

Compositions and methods for inducing an immune response

Heterocyclic compounds having a relatively flexible backbone are used to create combinatorial libraries that permit screening for lead compounds and selection of drug candidates for a variety of uses in human and veterinary medicine as well as in agriculture. The compounds of the library generally differ in ring size and chirality of substituents on the ring. Also disclosed are methods for providing and screening these libraries, preferably in an automated or computerizable manner, such as by using a computer program to virtually screen the compounds in order to identify those that are predicted to have bioactive conformations that should give rise to desirable biological effects.

Heterocyclic compounds, combinatorial libraries thereof and methods of selecting drug leads

Novel backbone cyclized peptide analogs are formed by means of bridging groups attached via the alpha nitrogens of amino acid derivatives to provide novel non-peptidic linkages. Novel building units disclosed are N(&#x3c9;-functionalized) amino acids constructed to include a spacer and a terminal functional group. One or more of these N(&#x3c9;-functionalized) amino acids are incorporated into a peptide sequence, preferably during solid phase peptide synthesis. The reactive terminal functional groups are protected by specific protecting groups that can be selectively removed to effect either backbone-to-backbone or backbone-to-side chain cyclizations. The invention is specifically exemplified by backbone cyclized bradykinin antagonists having biological activity. Further embodiments of the invention are somatostatin analogs having one or two ring structures involving backbone cyclization.

Conformationally constrained backbone cyclized peptide analogs

A method of inhibiting cell proliferation in a patient suffering from such disorder comprising administering to said patient an effective amount of a composition comprising, in admixture with a pharmaceutically acceptable carrier, a compound, or a pharmaceutically acceptable salt thereof, which is a substituted styrene compound which can also be a naphthalene, an indane or a benzoxazine; including nitrile and molononitrile compounds, and pharmaceutical compositions comprising, in admixture with a pharmaceutically acceptable carrier, a pharmaceutically-effective amount of such compound.

Styryl compounds which inhibit EGF receptor protein tyrosine kinase

The design and the synthesis of backbone cyclic peptide analogs which functionally mimic the nuclear localization signal (NLS) region of macromolecules is disclosed. The principles of the invention are exemplified for the NLS sequences of the human immunodeficiency virus type 1 proteins MA, Vpr, Tat and NLS-like sequences of HIV-1 protein Vif. We disclose the discovery of a novel, highly potent backbone cyclic peptide, designated BCvir, which inhibits nuclear import with an IC value of 35 nM. This inhibitory potency is to be compared to 12 &mgr;M exhibited by the linear parent HIV-1 MA NLS peptide. BCvir also reduced HIV-1 production by 75% in infected non-dividing cultured human T-cells and was relatively resistant to tryptic digestion. These properties render backbone cyclic peptide analogs of NLS or NLS-like sequences as candidates for novel drugs based on blocking nuclear import of viral genomes.

Inhibition of nuclear import by backbone cyclic peptide analogs

Novel backbone cyclized peptide analogs are formed by means of bridging groups attached via the alpha nitrogens of amino acid derivatives to provide novel non-peptidic linkages. Novel building units disclosed are N (&ohgr;-functionalized) amino acids constructed to include a spacer and a terminal functional group. One or more of these N (&ohgr;-functionalized) amino acids are incorporated into a peptide sequence, preferably during solid phase peptide synthesis. The reactive terminal functional groups are protected by specific protecting groups that can be selectively removed to effect either backbone-to-backbone or backbone-to-side chain cyclizations. The invention is specifically exemplified by backbone cyclized bradykinin antagonists having biological activity. Further embodiments of the invention are somatostatin analogs having one or two ring structures involving backbone cyclization.

Novel backbone cyclized peptide analogs are formed by means of bridging groups attached via the alpha nitrogens of amino acid derivatives to provide novel non-peptidic linkages. Novel building units disclosed are N,(&ohgr;-functionalized) amino acids constructed to include a spacer and a terminal functional group. One or more of these N,(&ohgr;-functionalized) amino acids are incorporated into a peptide sequence, preferably during solid phase peptide synthesis. The reactive terminal functional groups are protected by specific protecting groups that can be selectively removed to effect either backbone-to-backbone or backbone-to-side chain cyclizations. The invention is specifically exemplified by backbone cyclized bradykinin antagonists having biological activity. Further embodiments of the invention are somatostatin analogs having one or two ring structures involving backbone cyclization.

Growing community of inventors

Jerusalem, Israel

Chaim Gilon