Abstract: Analogs of SRIF which are selective for SSTR1 in contrast to the other cloned SRIF receptors. These analogs are useful in determining the tissue and cellular expression of the receptor SSTR1 and its biological role in the endocrine, exocrine and nervous system, as well as in regulating tumor growth. SRIF analog peptides, such as des-AA1,2,5[D-Trp8, N?MeIAmp9, Tyr11]-SRIF and counterparts incorporating Cbm at the N-terminus and/or N?Ser13, inhibit the binding of a universal SRIF radioligand to the cloned human receptor SSTR1, but they do not bind with significant affinity to human SSTR2, SSTR3, SSTR4 or SSTR5. By incorporating an iodinated tyrosine in position-2 or in position-11 in these SSTR1-selective SRIF analogs, a labeled compound useful in drug-screening methods is provided. The N-terminus accommodates bulky moieties without loss of selectivity, and a carbamoyl moiety or a conjugating agent that will accept a radioactive nuclide or will link to a cytotoxin may be present at the N-terminus.

Abstract: A process for the preparation of biologically active somatotropin from inclusion bodies of a recombinant host cell containing an inactive form of said somatotropin protein comprises the steps of: (a) contacting the inclusion bodies with an aqueous alcohol solution at an alkaline pH to solubilize said protein; and (b) bringing the solubilized protein into contact with a mild oxidizing agent to refold and form intramolecular disulfide bonds between cysteine residues of said protein.

Abstract: A polypeptide of the formula (I), Pa-L-Pb-L-Pc-L-Pd.

Abstract: Novel peptides which are conformationally constrained backbone cyclized somatostatin analogs, having somatostatin receptor subtype selectivity are disclosed. These patterns or receptor subtype selectivity provide compounds having improved therapeutic utility. Methods for synthesizing the somatostatin analogs and for screening of the somatostatin analogs are also disclosed. Furthermore, pharmaceutical compositions comprising somatostatin analogs, and methods of using such compositions are disclosed.

Abstract: A novel class of analogs which exhibit both high affinity and selectivity for Neuromedin B and Somatostann receptors are claimed. One example is Nal-Tyr-cyclo(D-Cys-D-Trp-Lys-D-Cys)-Abu-Nal-NH2.

Abstract: The present invention is directed to cyclic peptides of formula (I): X-A1-cyclo(D-Cys-A3-A4-Lys-A6-A7)-A8-Y, or a pharmaceutically acceptable salt thereof. The peptides bind selectively to the somatostatin subtype receptor type-5 and elicit an agonist effect from the somatostatin subtype receptors.

Abstract: Genetically-encodable, environmentally-responsive fusion proteins comprising ELP peptides. Such fusion proteins exhibit unique physico-chemical and functional properties that can be modulated as a function of solution environment. The invention also provides methods for purifying the FPs, which take advantage of these unique properties, including high-throughput purification methods that produce high yields (e.g., milligram levels) of purified proteins, thereby yielding sufficient purified product for multiple assays and analyses. The high throughput purification technique is simpler and less expensive than current commercial high throughput purification methods, since it requires only one transfer of purification intermediates to a new multiwell plate.

Abstract: The present invention features MCH antagonists active at the MCH-1R. The antagonists are optionally modified peptides able to inhibit the effect of MCH at MCH-1R. MCH antagonists have a variety of uses including being used as a research tool and being used to achieve a beneficial effect in a subject.

Abstract: The present invention relates to novel somatostatin analogues of the general formula (I) wherein Z may be absent or present and when present is selected from the group consisting of DOTA- and DTPA-based chelators, NOTA-based chelators, cabonyl compounds, hydrazino nicotinamide (hynic), N4-chelators, desferrioxamin, NxSy-chelators, all optionally complexed or labeled with a radioisotope, Tyrosine (Tyr) for halogenation, a fluorescent dye or biotin; L may or may not be present and is a linker molecule; X1 is a symmetric or asyrnmetric diamino acid, containing 3 or 4 consecutive C atoms with a linker to the chelating agent, for example D/L-diamino butyric acid (D/L-Dab) for a more basic character or D/L-Glu for coupling to primary and secondary amino groups; X2 is a positively charged natural or unnatural amino acid or arginine mimic or citrulline, or a neutral amino acid like Asn; X3 is phenylalanine (Phe), Ala-[3-(2-thienyl)] or &agr;-,&bgr;-naphthylalanine; X4 is an aromatic amino acid, optionally h

Abstract: Novel somatostatin polypeptides derived from Oncorhynchus mykiss, polynucleotides encoding novel somatostatin polypeptides, and methods for identifying bioactive modified somatostatin polypeptides.

Abstract: Disclosed is a series of somatostatin-dopamine chimeric analogs which retain both somatostatin and dopamine activity in vivo.

Abstract: The present invention relates to a method of inhibiting fibrosis in a patient. The method comprises administering a therapeutically effective amount of a somatostatin, a somatostatin agonist or a pharmaceutically acceptable salt thereof to said patent.

Abstract: The invention relates to compounds having a binding affinity for both the &agr;v&bgr;3 receptor and a (neuro)peptide receptor, in particular the somatostatin receptor, which compound comprises a first peptide part comprising at least once the amino acid sequence Arg-Gly-Asp, and a second peptide part coupled thereto, optionally via a linker, which second peptide part is a (neuro)peptide.

Abstract: The subject invention relates to the use of ascorbic acid and derivatives thereof in stabilizing radiolabeled proteins and peptides against oxidation loss of radiolabel and autoradiolysis. Ascorbic acid is added after radiolabeling, including any required incubation period, but prior to patient administration.

Abstract: Novel radiodiagnostic and radiotherapeutic peptides which are conformationally constrained backbone cyclized somatostatin analogs, having improved somatostatin receptor subtype affinity and selectivity are disclosed. The backbone cyclized peptide analogs disclosed possess unique and superior properties over other analogs, such as chemical and metabolic stability, selectivity, increased bioavailability and improved pharmacokinetics. Furthermore, the unique patterns of receptor subtype selectivity provide compounds having improved diagnostic and therapeutic utilities. Pharmaceutical compositions comprising the backbone cyclized somatostatin analogs and radiolabelled analogs, reagents for synthesizing same, and methods of using such compositions for radiodiagnostic and radiotherapeutic purposes are also disclosed.

Abstract: The invention features somatostatin antagonists having a D-amino acid at the second residue.

Abstract: The invention relates to a peptide compound having an improved binding affinity to somatostatin receptors, comprising a somatostatin analogue as the peptide and a chelating group covalently linked to the N-terminal free amino group of said peptide, wherein said somatostatin analogue carries an 1-naphthylalanine or a 3-benzothienylalanine residue in its 3-position. The invention further relates to said peptide compound labeled with a detectable element or with a therapeutic radionuclide, as well as to a diagnostic method and to a method for the therapeutic treatment of tumors, by using the labeled compounds.

Abstract: Disclosed are lanthionine bridged peptides having the structure methods of their preparation and their use as pharmacologically active agents.

Abstract: Acylcarnitines, such as L-acetylcarnitine (I) were found to have marked antitumour activity, which can be further increased by simultaneous administration of somatosstatin.

Abstract: Stable analogs of cyclic peptides containing disulfide linkages are disclosed. The disulfide linkage is modified by one of four methods: (a) sulfide contraction, (b) isosteric substitution, (c) thioketal expansion, or (d) alkylation expansion. In sulfide contraction the disulfide bond (—S—S—) is replaced with a monosulfide bond (—S—) in which a bifunctional effector molecule, such as a ligand or chemotoxic agent, is bound to the new peptide linkage. In isosteric substitution, one sulfur atom is replaced with a carbon atom and at least one of the carbon atoms at the modified site is a bifunctional effector molecule. In thioketal expansion, an alkylidene unit (—CR1C2—) is inserted between the two sulfur atoms. In alkylation expansion, an alkyl moiety of from C2 to C3, is inserted between the two sulfur atoms.

Abstract: Administration of a radioisotopic compound by infusion over a period of time greater than two hours, preferably greater than twelve hours, greatly increases the maximum radioactivity that accumulates in the target cell. The efficacy of the administration of the radiolabeled compound can be increased about five times higher than prior bolus injection or short infusion methods. This method enhances the tumor to background ratio by increasing the actual radioligand accumulated inside the target cells. This technique works for any radiolabeled compound whose cellular uptake is limitedly a cellular process of either binding to a cellular receptor or to a transport protein. Once the radiolabeled compound is bound and internalized, the ability of an unlabeled compound to compete with the radioligand is markedly decreased. The primary factor governing residence time after internalization is the physical half-life of the radioisotope, not biologic half-life.

Abstract: The present invention is directed to cyclic derivatives containing an imidazole cis amide bond mimetic which bind selectively to somatostatin receptor subtypes and the use thereof in treating conditions which can be treated by eliciting an agonist or antagonist effect from the somatostatin subtype receptors. This invention is also directed to methods for making the compounds of the instant invention.

Abstract: Analogs of SRIF which are selective for SSTR3 in contrast to the other cloned SRIF receptors. These analogs are useful in determining the tissue and cellular expression of the receptor SSTR3 and its biological role in the endocrine, exocrine and nervous system, as well as in regulating tumor growth. SRIF analog peptides, such as des-AA1,2,4,5,12,13[N&bgr;MeD-Agl8(2-naphthoyl) ]-SRIF and counterparts incorporating D-Cys3 and/or Tyr7, inhibit the binding of a universal SRIF radioligand to the cloned human receptor SSTR3, but they do not bind with significant affinity to human SSTR1, SSTR2, SSTR4 or SSTR5. By incorporating an iodinated tyrosine in position-2 or in position-11 in these SSTR3-selective SRIF analogs, a labeled compound useful in drug-screening methods is provided. Because the N-terminus accommodates bulky moieties without loss of selectivity, a cytotoxin or a complexing agent to accept a radioactive nuclide may be present at the N-terminus.

Abstract: This invention relates to immunogenic, non-naturally occurring peptides and immunologically reactive molecules thereto which modulate the activity of hormones or the receptors therefor. Methods of modulating hormonal activity in an animal and compositions therefor are also contemplated.

Abstract: A stable pharmaceutical formulation for intravenous or intramuscular administration of Octreotide, which is characterized in that the vehicle for injection of the peptide or pharmaceutically acceptable salts thereof contains glycine in concentrations ranging from 10 to 60 mM and aqueous solution of hydrochloric acid in sufficient quantity to adjust the pH of the formulation to values between 3.0 and 4.2.

Abstract: A pharmaceutical composition and method, for treating human or non-human neoplastic disorders, e.g. colorectal disorders, comprising the administration of pharmaceutically effective amounts of galanin, octreotide and serotonin in a pharmaceutically acceptable carrier. The effective amount is 10 &mgr;g/kg body weight to about 60 &mgr;g/kg body weight of each of the three, preferably about 10 &mgr;g/kg to about 20 &mgr;g/kg of each of the three.

Abstract: The invention relates to the use of peptides individually or in combination, for treating and/or preventing angiogenesis. It also relates to the use of peptide analogs or a combination of peptides referred to as MuJ-7 as anticancer drugs in restricting the tumor growth and spread by inhibiting tumor angiogenesis. MuJ-7, in addition inhibits metastasis through its antiangiogenic activity in all cancers. The invention also relates to a pharmaceutical composition containing either individual peptides or in combination, and methods of treatment of human beings and animals for curing and/or preventing angiogenesis.

Abstract: The current invention provides methods for molecule purification by RP-LC and RP-HPLC that uses unbranched terminal alkyldiols as eluting solvents. In particular, the present invention purifies molecules, particularly proteins and peptides, on reverse phase liquid chromatography columns using a buffer containing either 1,5 pentanediol, 1,6 hexanediol or 1,7 heptanediol.

Abstract: Analogs of SRIF which are selective for SSTR1 in contrast to the other cloned SRIF receptors. These analogs are useful in determining the tissue and cellular expression of the receptor SSTR1 and its biological role in the endocrine, exocrine and nervous system, as well as in regulating tumor growth. SRIF analog peptides, such as des-AA1,2,5[D-Trp8, NMeIAmp9, Tyr11]-SRIF and counterparts incorporating Cbm at the N-terminus and/or N&agr;Ser13, inhibit the binding of a universal SRIF radioligand to the cloned human receptor SSTR1, but they do not bind with significant affinity to human SSTR2, SSTR3, SSTR4 or SSTR5. By incorporating an iodinated tyrosine in position-2 or in position-11 in these SSTR1-selective SRIF analogs, a labeled compound useful in drug-screening methods is provided. The N-terminus accommodates bulky moieties without loss of selectivity, and a carbamoyl moiety or a conjugating agent that will accept a radioactive nuclide or will link to a cytotoxin may be present at the N-terminus.

Abstract: This invention relates to immunogenic, non-naturally occurring peptides and immunologically reactive molecules thereto which modulate the activity of hormones or the receptors therefor. Methods of modulating hormonal activity in an animal and compositions therefor are also contemplated.

Abstract: This invention relates a process for preparing octreotide and derivatives thereof. The starting material, Thr(ol)(tBu)-2-chlorotrityl resin is coupled with the various amino acids. The straight peptide-resin of D-Phe-Cys(Trt)-Phe-D-Trp(Boc)-Lys(Boc)-Thr(tBu)-Cys(Trt)-Thr(ol)(tBu)-2-chlorotrityl resin or D-Phe-Cys(Trt)-Tyr(tBu)-D-Trp(Boc)-Lys(Boc)-Thr(tBu)-Cys(Trt)-Thr(ol)(tBu)-2-chlorotrityl resin was obtained. Cleavage of the peptide from the resin was achieved by strong acid solution.

Abstract: The present invention relates to a method of treating hyperlipidemia and to reducing triacylglycerols. glycerol and cholesterol in a patient. The method includes the step of administering a therapeutically effective amount of a type-5 selective somatostatin agonist to said patient. A pharmaceutical composition comprises said agonist and such product is used in the preparation of the composition for use in treating hyperlipidemia or reducing triacylglycerols, glycerol and cholesterol in a patient's body.

Abstract: The invention features novel somatostatin analogs that may be readily labeled with toxic or non-toxic detectable labels. These unlabeled and labeled analogs are useful for specifically targeting somatostatin receptor bearing cells, in particular neoplastic cells. Labeled analogs are useful, for example, for tumor localization and detection. Where labeled with a toxic label (e.g., radioactivity), the analogs are useful for the targeted delivery of toxicity to somatostatin receptor-bearing cells, in particular neoplastic cells. Also disclosed are methods for treating and detecting neoplasms, and methods for imaging somatostatin receptor-bearing cells.

Abstract: Polysaccharide-somatostatin analogs of the formula: wherein the somatostatin analog is directly or indirectly coupled from a terminal N-amino group of the somatostatin analog to a polysaccharide, and the polysaccharide-somatostatin analog is provided with an effective negative charge. The compounds are useful in diagnosing and treating cancers.

Abstract: This invention relates to immunogenic, non-naturally occurring peptides and immunologically reactive molecules thereto which modulate the activity of hormones or the receptors therefor. Methods of modulating hormonal activity in an animal and compositions therefor are also contemplated.

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: Ureins are obtained by reaction, in basic medium, between an N&ohgr;-(aryloxycarbonyl)diamino acid and a compound containing a free amino group. The chirality of the compounds is outstandingly well preserved.

Abstract: A combination of a compound of the somatostatin class and a rapamycin macrolide is useful for the prevention or treatment of cell hyperproliferation.

Abstract: The invention provides novel peptide-based pharmacophores and compounds which bind somatostatin receptors with high affinity and which exhibit improved pharmacokinetic properties over known somatostatin analogs. The pharmacophores and compounds of the invention may be used in labeled or unlabeled form for diagnosing and/or treating somatostatin responsive diseases. The invention also provides radiopharmaceuticals and kits comprising these compounds, as well as methods for diagnosing and/or treating somatostatin receptor mediated diseases.

Abstract: Novel peptides which are conformationally constrained backbone cyclized somatostatin analogs. Methods for synthesizing the somatostatin analogs and for producing libraries of the somatostatin analogs are also disclosed. Furthermore, pharmaceutical compositions comprising somatostatin analogs, and methods of using such compositions are disclosed.

Abstract: A procedure for obtaining the somatostatin analog, octreotide by means of solid phase synthesis on polymer supports and by intervention of protector groups of the Fmoc/tBu type. It includes construction of the seven amino acid, Boc-D-Phe-Cys(Trt)-Phe-D-Trp-Lys(Boc)Thr(tBu)-Cys(Trt)-Cl-trityl-R linear peptide, in which R is a polymer; treatment of the resulting peptidyl-resin with acid, for detachment of the peptide from the resin; cycling the linear structure obtained by reaction with iodine before or after incorporation of the threoninol residue into the terminal carboxy end; incorporating the threoninol residue in solution upon the seven amino acid protected peptide with or without the disulfide bridge formed; and removing the protections at the N-terminus and at the side chains with a treatment with 70-95% TFA in presence of scavengers to obtain octreotide.

Abstract: The present invention encompasses novel peptides that are agonists to somatostatin and the use of the agonists for treatment of cancer. The invention particularly relates to the design and synthesis of novel analogs of somatostatin incorporating &agr;, &agr;-dialkylated amino acids in a site specific manner. The invention encompasses methods for the generation of these peptides, compositions containing the peptides and the pharmacological applications of these peptides especially in the treatment and prevention of cancer.

Abstract: Chimeric polypeptides having the immunogenicity of somatostatin include an amino acid sequence of somatostatin-14 and a protein carrier. The sequence of somatostatin-14 is joined to the 3′-end of the protein carrier by a spacer (Sp)n, wherein Sp consists of an alkaline amino acid and an amino acid that provides a rigid expended chain-like &bgr;-structure, and n designates the number of blocks in the spacer. In a preferred embodiment, n is from 1 to 8 and the protein-carrier is chloramphenicol acetyl transferase (CAT).

Abstract: The present invention provides a method for chemically removing a N-terminal methionine residue selectively, specifically and efficiently from a peptide or a salt thereof having an optionally oxidized methinine residue at its N-terminal. The method reacts a peptide or a salt thereof having an optionally oxidized methinine residue at its N-terminal with an &agr;-diketone derivative, followed by hydrolysis.

Abstract: Protein suspensions comprising soluble and insoluble components are purified via flocculation with anionic polymers, such as polyacrylamides, potato starch, or modified cellulose. The procedure improves the efficiency of solid/liquid separations and can minimize or eliminate the requirement for centrifugation and/or filtration in large scale biotechnological processes. The method is particularly well suited for the purification and clarification of protein suspensions containing soluble somatotropin monomer using polyacrylamide and polysaccharide flocculants.

Abstract: Novel somatostatin polypeptides derived from Oncorhynchus mykiss, polynucleotides encoding novel somatostatin polypeptides, and methods for identifying bioactive modified somatostatin polypeptides.

Abstract: Peptides are provided with the properties of enhancing the migration and adhesion of bone-forming cells to a substrate, useful for promoting bone mineralization and osseointegration in the healing of, for example, orthopedic surgical procedures.

Abstract: The present invention relates to a method of inhibiting fibrosis in a patient. The method comprises administering a therapeutically effective amount of a somatostatin, a somatostatin agonist or apharmaceutically acceptable salt thereof to said patient.

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: The invention features somatostatin antagonists having a D-amino acid at the second residue.