Abstract: The synthesis and elucidation of nineteen heterocyclic or halophenyl amide erivatives of dolastatin 10 are disclosed. These compounds and the methods of producing those compounds offer demonstrated significant in vitro activity against several human cancer cell lines. These compounds and the methods of producing those compounds offer a commercially viable alternative to natural and synthetic dolastatin 10.

Abstract: Synthetic peptide analogs of human kininogen are provided which are conformationally restricted by means of intramolecular bonding. The peptides mimic the biological activity of human kininogen by inhibiting the activity of the biologically significant protease, calpain. The peptides are designed by means of an equilibrium conformational model of the kininogen heavy chain.

Abstract: The invention relates to radiolabeled imaging of a mammalian body. The invention in particular provides for reagents labeled with technetium-99m for such imaging. The invention provides peptides which bind technetium-99m and which can be targeted to specific sites within a mammalian body.

Abstract: The membrane permeating antibacterial peptide, PR-39, previously found only in the intestine, was purified from wound fluid and shown to possess syndecan-1 and syndecan-4 inductive activity specifically in mesenchymal cells. This is a newly recognized function that defines peptide containing syndecan-inducing activity, and that are known as synducins. Therefore a molecule with both antimicrobial and synducin activities is deposited in wounds where it can simultaneously reduce infection and influence the action of growth factors, matrix components, and other cellular effectors involved in wound repair. Synducins, including PR-39, and derivatives thereof, is therefore useful in the modulation of wound healing, as well as other disorders involving mesenchymal cells and cell surface molecular interaction, including metastatic disease, angiogenesis, restenosis, stasis or decubitis ulcers, and prevention of keloids.

Abstract: A physiologically active substance well capable of permeating biomembrane according to the present invention is represented by: ##STR1## where R represents a residue of a physiologically active substance comprising a peptide, amino acid, aliphatic amine having a phenol skeleton, amino sugar, nucleoside or lactam compound and a residue of physiologically active derivative thereof. The biomembrane permeability of a substance with poor biomembrane permeability can be improved by introducing an adamantyl group to the physiologically active substance.

Abstract: The present invention provides peptides having an amino acid sequence that is the amino acid sequence of a human bactericidal/permeability-increasing protein (BPI) functional domain or a subsequence thereof, and variants of the sequence or subsequence thereof, having at least one of the BPI biological activities, such as heparin binding, heparin neutralization, LPS binding, LPS neutralization or bactericidal activity. The invention provides peptides and pharmaceutical compositions of such peptides for a variety of therapeutic uses.

Abstract: Peptides which act as inhibitors or substrates of thrombin are derived from the formula: D-Phe-Pro-Arg or its analogues, wherein Phe is substituted by (a), wherein Ar.sub.1 or Ar.sub.2 are the same or different and are selected from the group consisting of phenyl, thienyl, pyridyl, naphthyl, thionaphtyl, indolyl and saturated groups corresponding to these, optionally substituted by up to three groups selected from C.sub.1 -C.sub.3 alkyl and C.sub.1 -C.sub.3 alkoxy, L.sub.1 and L.sub.2 are the same of different and are selected from the group consisting of CH.sub.2, C.sub.2 --C.sub.2, O-CH.sub.2, S-CH.sub.2, Ar-L taken together optionally means H, diphenyl-methyl, fluorenyl or saturated groups corresponding to these, but one of the Ar-L cannot be H when the other [CH.sub.2 ].sub.n -Q, (c) where Q=H, amino, amidino, imidazole, guanidino or isothioureido and n=1-5, preferably 3-5, or C.sub.3 -C.sub.9 alkyl and C.sub.5 -C.sub.

Abstract: The invention provides RGD containing peptides which are cyclized and contain hydrophobic moieties adjacent the carboxy terminus of the RGD sequence. Such peptides have an high affinity for the receptor IIb/IIIa and low affinity for the fibronectin and vitronectin receptors. Such peptides can be administered in a suitable physiologically acceptable carrier to therapeutically treat thrombosis.

Abstract: Disclosed herein are pentapeptide derivatives of the formula (SEQ ID NO: 24) XNR.sup.1 --CH(R.sup.2)--C(O)--NH--CH(R.sup.3 --C(O)--NR.sup.4 --CH(CH.sub.2 Y)--CO--NH--CH[CR.sup.5 (R.sup.6)--COOH]--C(W)--NH--CH(R.sup.7)--Z wherein X is a terminal group, for example, alkanoyl or phenylalkanoyl radicals, R.sup.1 is alkyl or phenylalkyl, R.sup.2, R.sup.3 and R.sup.7 are selected from the side chains of amino acid or derived amino acid residues, R.sup.4, R.sup.5, and R.sup.6 are hydrogen or lower alkyl, W is oxo or thioxo, Y is carboxy, carbamyl or 5-1H-tetrazolyl and Z is carboxy or 5-1H-tetrazolyl. The derivatives are useful for treating herpes infections.

Abstract: A method to obtain selected individual peptides or families thereof which have a target property and optionally to determine the amino acid sequence of a selected peptide or peptides to permit synthesis in practical quantities is disclosed. In general outline, the method of the invention comprises synthesizing a mixture of randomly or deliberately generated peptides using standard synthesis techniques, but adjusting the individual concentrations of the components of a mixture of sequentially added amino acids according to the coupling constants for each amino acid/amino acid coupling. The subgroup of peptides having the target property can then be selected, and either each peptide isolated and sequenced, or analysis performed on the mixture to permit its composition to be reproduced. Also included in the invention is an efficient method to determine the relevant coupling constants.

Abstract: Novel antagonists of endothelin are described, as well as methods for the preparation and pharmaceutical compositions of the same, which are useful in treating elevated levels of endothelin, acute and chronic renal failure, hypertension, myocardial infarction, metabolic, endocrinological, neurological disorders, congestive heart failure, endotoxic shock, subarachnoid hemorrhage, arrhythmias, asthma, preeclampsia, Raynaud's disease, percutaneous transluminal coronary angioplasty or restenosis, angina, cancer, pulmonary hypertension, ischemic disease, gastric mucosal damage, ischemic bowel disease, and diabetes.

Abstract: Tripeptides capable of regulating the function of cells of the mammalian immune and/or central nervous system, pharmaceutical compositions containing the peptides and methods of use thereof are provided.

Abstract: The invention relates generally to peptides which decrease the half-life of active plasminogen activator inhibitor-1. This invention further relates to methods and compositions for using peptides which decrease the half-life of active plasminogen activator inhibitor-1. Further, the invention includes methods and compositions useful in clot lysis.

Abstract: Compositions of the invention include composites comprising a biomaterial having compounds thereon with enhanced cell binding with respect to collagen. These composites are useful for soft and hard tissue repair or reconstruction and for in vitro uses. Suitable compounds with enhanced cell binding include synthetic peptides that mimic the conformation necessary for recognition and docking of collagen binding species (such as cell surface receptors for collagen and fibronectin) and have the amino acid residues -Ile-Ala- folded in a .beta.-bend.

Abstract: Calcitonin gene-related peptide regulate immune cell function and cytokine release and are useful in the treatment of immune cell and cytokine mediated, immune mediated diseases, such as rheumatoid arthritis, treating viral infections, tumors and organ transplants.

Abstract: Certain toxic compounds (T) such as, for example, compounds based upon diphtheria toxin, ricin toxin, pseudomonas exotoxin, .alpha.-amanitin, pokeweed antiviral protein (PAP), ribosome inhibiting proteins, especially the ribosome inhibiting proteins of barley, wheat, corn, rye, gelonin and abrin, as well as certain cytotoxic chemicals such as, for example, melphalan and daunomycin can be conjugated to certain analogs of gonadotropin-releasing hormone to form a class of compounds which, when injected into an animal, destroy the gonadotrophs of the animal's anterior pituitary gland. Hence such compounds may be used to sterilize such animals and/or to treat certain sex hormone related diseases.

Abstract: Compositions and methods for prevention of adhesion formation, whereby an effective amount of one or more adhesion preventing RGD-containing peptides is administered for a period of time sufficient to permit tissue repair. The RGD-containing peptide is further characterized in that it inhibits platelet aggregation and does not induce inflammation or trauma at the site of administration. The RGD-containing peptide is preferably administered in conjunction with a delivery vehicle (e.g., microcapsules, microspheres, liposomes, viscous instillates and absorbable mechanical barriers) useful for maintaining local concentrations of the peptide at an effective level.

Abstract: Disclosed is a method for transporting neurologic therapeutic agents to the brain by means of the olfactory neural pathway and a pharmaceutical composition useful in the treatment of brain disorders.

Abstract: Synthetic pulmonary surfactants having antioxidant properties consisting of a complex of a polypeptide of 3-4 amino acid residues, with an antioxidant moiety, and a lipid consisting of one or more of the lipids associated with natural pulmonary surfactant were prepared. These surfactants are useful in the treatment of respiratory distress syndrome.

Abstract: The invention provides compounds of the general formula: ##STR1## The compounds have hemoregulatory activities and can be used to stimulate haematopoiesis and for the treatment of viral, fungal and bacterial infectious diseases.