Abstract: The present invention relates to novel peptide sequences, compositions and methods for controlling fish reproduction. More particularly, the invention provides novel Neurokinin B peptides NKF and NKB and analogues thereof that regulate reproduction in fish. The invention further provides preprohormone thereof comprising at least one of a first peptide fragment of the amino acid sequence X1-X2-X3-X4-X5-X6-Asp7-X8-Phe9-Val10-X11-Leu12-Met13 and a second peptide fragment of the amino acid sequence of Glu1-Met2-His3-Asp4-Ile5-Phe6-Val7-Gly8-Leu9-Met10 and variants thereof, nucleic acid sequences and novel fish NKB receptors.

Abstract: Peptide helices stabilized by backbone cyclization which are capable of inhibiting dimerization of the Chemokine (C-C motif) receptor 2 (CCR2), as well as pharmaceutical compositions including such backbone cyclized peptide helices. Use of pharmaceutical compositions and peptide helices in treatment of Multiple Sclerosis (MS) and other diseases associated with CCR2 activation.

Abstract: 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.

Abstract: 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.

Abstract: The present invention relates to backbone cyclized CD-4 mimetics and to compositions and methods comprising them for preventing and treating viral infection. In particular, the present invention relates to orally bio-available compounds and formulations for prevention and treatment of human HIV-1 infection.

Abstract: 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.

Abstract: 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.

Abstract: The present invention is directed to compositions and methods of preventing for treating a retroviral infection, more particularly an HIV (human immunodeficiency virus) infection, and even more particularly an HIV-1 infection. The compositions and methods involve molecules that mimic the active site of the human CD4 protein.

Abstract: Backbone cyclized peptides which are ?-melanocortin stimulating hormone (?MSH) analogs, having improved Melanocortin-4 receptor agonist activity are disclosed. The backbone cyclized peptide analogs disclosed possess unique and superior properties over other analogs, such as metabolic stability, increased oral bioavailability, improved intestinal permeability and pharmacological activity in-vivo. Pharmaceutical compositions that include the backbone cyclized ?MSH analogs, and methods of using such compositions for the treatment of metabolic disorders including obesity are also disclosed.

Abstract: 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?(?-functionalized) amino acids constructed to include a spacer and a terminal functional group. One or more of these N?(?-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.

Abstract: A conjugate of a histone moiety covalently attached to a macromolecule-of-interest, in which the histone moiety is transportable through the cell membrane and importable into the cell nuclei, is disclosed. Further disclosed are chemical and recombinant methods of preparing such a conjugate, pharmaceutical compositions containing same and uses thereof for delivering therapeutically active macromolecules into cells. A novel method for quantitatively determining a cytoplasmic uptake and/or a nuclear uptake of a moiety into cells is also disclosed.

Abstract: 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.

Abstract: Backbone cyclized peptide analogs that include at least one building unit of a C?(?-functionalized) amino acid that is constructed to include a spacer and a terminal functional group. The bridging groups are attached via alpha carbons of amino acid derivatives to provide novel non-peptide linkages. Also disclosed are novel C?(?-functionalized) amino acid building units, and methods of preparing them as well as the cyclized peptide analogs, preferably during solid phase peptide synthesis. The reactive terminal functional groups are protected by specific protecting groups that can be selectively removed to effect the desired cyclization.

Abstract: Novel diagnostic and therapeutic peptides disclosed herein are somatostatin analogs backbone cyclized through metal complexation, and having improved somatostatin receptor subtype affinity and selectivity. These backbone cyclized peptide analogs possess unique and superior properties over other analogs, including chemical and metabolic stability, selectivity, increased bioavailability and improved pharmacokinetics. Pharmaceutical compositions that include these backbone cyclized somatostatin analogs, radiolabelled analogs, reagents for synthesizing same, and methods of using such compositions for diagnostic and therapeutic purposes are also disclosed.

Abstract: 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 IC50 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.

Abstract: The present invention provides according to a first of its aspects, new compounds that have a flexible scaffold with various degrees of conformational restriction and accordingly are useful as drug candidates. These compounds may be used to produce new combinatorial libraries that will permit to screen for and select drug candidates for a variety of uses in human medicine, veterinary medicine and in agriculture.

Abstract: 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&agr;(&ohgr;-functionalized) amino acids constructed to include a spacer and a terminal functional group. One or more of these N&agr;(&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.

Abstract: 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&agr;(&ohgr;-functionalized) amino acids constructed to include a spacer and a terminal functional group. One or more of these N&agr;(&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.

Abstract: 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&agr;(&ohgr;-functionalized) amino acids constructed to include a spacer and a terminal functional group. One or more of these N&agr;(&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.

Abstract: 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.