Abstract: Cyclic constructs with an N-terminus and a C-terminus which bind to a natriuretic peptide receptor and include a plurality of amino acid residues, at least one amino acid surrogate of formula I: where R, R?, Q, Y, W, Z, J, x and n are as defined in the specification, and optionally at least one prosthetic group, pharmaceutical compositions including such cyclic constructs, and methods of treating congestive heart failure or other conditions, syndromes or diseases for which induction of anti-hypertensive, cardiovascular, renal or endocrine effects are desired.

Abstract: Melanocortin receptor-specific pyrrolidine compounds having the structure: and stereoisomer and pharmaceutically acceptable salts thereof, where R1, R2, and R3 are as described in the specification, preferably where R3 is a D-amino acid with at least one substituted or unsubstituted phenyl or naphthyl aromatic ring, and where R3 optionally further includes an amine capping group or from one to three additional amino acid residues, optionally with an amine capping group, which compounds are agonists, antagonists or mixed agonists and antagonists at one or more melanocortin receptors, and having utility in the treatment of melanocortin receptor-related disorders and conditions. Methods of synthesis of compounds of structure (I), pharmaceutical compositions containing a compound of structure (I) and methods relating to the use thereof are also disclosed.

Abstract: Compounds of the general formula: or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, and X are as defined. Further provided are methods for treatment of sexual dysfunction, including erectile dysfunction and female sexual dysfunction, and combination drugs and method of use thereof, including a compound of the invention and one or more second sexual dysfunction pharmaceutical agents.

Abstract: Compounds of the general formula: or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, and X are as defined. Further provided are methods for treatment of sexual dysfunction, including erectile dysfunction and female sexual dysfunction, and combination drugs and method of use thereof, including a compound of the invention and one or more second sexual dysfunction pharmaceutical agents.

Abstract: Provided are methods for selecting melanocortin receptor-specific compounds for attenuating food intake and for treatment of specific disease conditions, including treatment of obesity and related energy homeostasis or feeding disorders characterized by excess weight gain, without inducing a sexual response, and methods for selecting compounds for treatment of sexual dysfunction. Further provided are pharmaceutical preparations defined by such methods, and methods and preparations for attenuating food intake and treatment of said conditions.

Abstract: Methods for selection of compounds for treatment of obesity, compounds selected by the disclosed methods, and methods of treatment of obesity, wherein a selective melanocortin-4 receptor compound is identified, which compound is further characterized in that it attenuates the binding of both an agonist, including alpha-melanocyte stimulating hormone, and an inverse agonist, including agouti-related protein, to a melanocortin receptor, including melanocortin-4 receptor.

Abstract: Linear and cyclic peptidomimetics which bind to one or more melanocortin receptors are provided, which peptidomimetics include at least one ring-constrained amino acid surrogate of formula I: where R1, R2, R3, R4, R5, R6, R7, R8, and y are as defined in the specification, together with methods for synthesizing ring-constrained amino acid surrogates of formula I and peptidomimetics incorporating the same, and methods of use of peptidomimetics in the treatment of various diseases, syndromes and conditions.

Abstract: A cyclic peptide of the structural formula: or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R5, R6, m, n and p are as defined. Further provided are compositions for treatment of sexual dysfunction in mammals, including male sexual dysfunction, such as erectile dysfunction, and female sexual dysfunction, by administration of a cyclic peptide including a C-terminus —OH group. Routes of administration include injection, oral, urethral, vaginal, nasal and mucosal administration.

Abstract: A melanocortin receptor-specific compound of the general formula of structure I: where X, R1, R2a, R2b, R3, R4a, R4b, R5a and R5b are as defined in the specification, which compound binds with high affinity to one or more melanocortin receptors and is optionally an agonist, an antagonist, an inverse agonist or an antagonist of an inverse agonist, and may be employed for treatment of one or melanocortin receptor-associated conditions or disorders, and methods for the use of the compounds of the invention.

Abstract: Metallopeptides with a sequence of a biologically active gamma-melanocyte stimulating hormone sequence of length n residues, wherein a residue including a nitrogen atom and sulfur atom each available for complexation to a metal ion is inserted at any position from between the two and three position to the C-terminus side of the n position, or alternatively is substituted for the residue at any position from the three position to the n position, with a metal ion complexed thereto, with any proline (Pro) residue which is either of the two residues on the immediately adjacent N-terminus side of the inserted or substituent residue comprising a nitrogen atom and sulfur atom available for complexation to a metal ion is substituted with a homolog.

Abstract: A melanocortin receptor-specific compound of the general formula of structure I: where X, R1, R2a, R2b, R3, R4a, R4b, R5a and R5b are as defined in the specification, which compound binds with high affinity to one or more melanocortin receptors and is optionally an agonist, an antagonist, an inverse agonist or an antagonist of an inverse agonist, and may be employed for treatment of one or melanocortin receptor-associated conditions or disorders, and methods for the use of the compounds of the invention.

Abstract: Methods for isolation of a synthetic cyclic peptide by spray drying, including spray drying at elevated temperatures, products made by the methods, and synthetic cyclic peptides preparations with defined characteristics, including an essentially amorphous acid addition salt of Ac-Nle-cyclo(-Asp-His-D-Phe-Arg-Trp-Lys)-OH in the form of a fine powder with a particle diameter of about 2 to about 20 microns.

Abstract: Method of making metallopeptides is provided, for use in biological, pharmaceutical and related applications. The metallopeptides are made of peptides, peptidomimetics and peptide-like constructs, and include a metal ion-binding region thereof which includes at least one orthogonal sulfur-protecting group, in which the peptide, peptidomimetic or construct is conformationally fixed on deprotection of the sulfur and complexation of the metal ion-binding region with a metal ion while the peptide, peptidomimetic or construct is cleavably bound to solid phase.

Abstract: Linear and cyclic peptides are provided specific to one or melanocortin receptors, and which exhibit agonist, antagonist, or mixed agonist-antagonist activity.

Abstract: Metallopeptide compositions are provided for treatment of sexual dysfunction in mammals, including male sexual dysfunction, such as erectile dysfunction, and female sexual dysfunction. The metallopeptides include at least one, and preferably two, aromatic amino acid side chain moieties, and are further characterized in that the metallopeptides preferably do not bind or significantly bind to a melanocortin receptor.

Abstract: Metallopeptides with a sequence of a biologically active alpha-melanocyte stimulating hormone (?-MSH), gamma-melanocyte stimulating hormone (?-MSH), or bombesin sequence of length n residues, wherein a residue including a nitrogen atom and sulfur atom each available for complexation to a metal ion is inserted at any position from between the two and three position to the C-terminus side of the n position, or alternatively is substituted for the residue at any position from the three position to the n position, with a metal ion complexed thereto, with any proline (Pro) residue which is either of the two residues on the immediately adjacent N-terminus side of the inserted or substituent residue comprising a nitrogen atom and sulfur atom available for complexation to a metal ion is substituted with a homolog.

Abstract: Melanocortin receptor-specific piperazine or ketopiperazine compounds having the structure: and stereoisomer and pharmaceutically acceptable salts thereof, where X is CH2 or C?O, R1, R2, and R3 are as described in the specification, preferably where R3 is a D-amino acid with at least one substituted or unsubstituted phenyl or naphthyl aromatic ring, and where R3 optionally further includes an amine capping group, a second amino acid residue or a second amino acid residue with an amine capping group, which compounds are agonists, antagonists or mixed agonists and antagonists at one or more melanocortin receptors, and having utility in the treatment of melanocortin receptor-related disorders and conditions. Methods of synthesis of compounds of structure (I), pharmaceutical compositions containing a compound of structure (I) and methods relating to the use thereof are also disclosed.

Abstract: The invention provides methods for identification and determination of target-specific sites in peptides and proteins, including a method for determining the primary sequence of a secondary structure within a known parent polypeptide that binds to the target of interest. In one embodiment of the invention, a residue or mimetic containing a nitrogen atom and a sulfur atom available for binding to a metal ion is serially substituted for single residues in or inserted between adjacent residues in a known primary sequence of a peptide or protein. The resulting sequence is complexed with a metal ion thereby forming a metallopeptide. The resulting metallopeptides are then used in binding or functional assays related to the target of interest, and the metallopeptide(s) which result in significant or substantially decreased or changed binding or functionality are determined to identify the primary sequence involved in such binding or functionality.

Abstract: There is provided compounds having the formula of structure I: wherein the groups —C(R8)(CH2)vCH(R9)(CH2)y-Q and —C(R8)(CH2)vCH(R9)(CH2)y-J are the same, and R1a, R1b, R2a, R2b, R8, R9, J, Q, W, X, L2, v and y have meanings given in the description. Thus use of such compounds in the treatment of a condition responsive to changes in melanocortin receptor function in a human or non-human mammal (e.g. male sexual dysfunction, female sexual dysfunction, an eating disorder, above optimal body weight, obesity, below-optimal body weight or cachexia) is also described.

Abstract: A highly selective melanocortin-4 receptor antagonist cyclic hexapeptide of the formula where R1, R2, R3a, R3b, R4, R5, x, y and z are as defined in the specification, and a method of treating body weight disorders, including cachexia, sarcopenia and wasting syndrome or disease, and treating inflammation and immune disorders.