Abstract: Method of making metallopeptide combinatorial libraries and metallopeptides are provided, for use in biological, pharmaceutical and related applications. The combinatorial libraries 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. Thereafter the library members may be screened to select those with the desired specificity and affinity.

Abstract: Metallopeptides and metallopeptide combinatorial libraries specific for opioids receptors are provided, for use in biological, pharmaceutical and related applications. The metallopeptides and combinatorial libraries are made of peptides, peptidomimetics and peptide-like constructs, in which the peptide, peptidomimetic or construct is conformationally fixed in a biologically active configuration specific for one or more opioid receptors on complexation of a metal ion-binding portion thereof with a metal ion.

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: Multiple agent therapy for treatment of sexual dysfunction, including male erectile dysfunction, with sequential administration a type V phosphodiesterase inhibitor (PDE-5), such as sildenafil, preferably wherein the PDE-5 inhibitor is administered by oral dose means, and a melanocortin 3 and/or 4 receptor agonist, such as Ac-Nle-cyclo(-Asp-His-D-Phe-Arg-Trp-Lys)-OH (PT-141) preferably wherein the PT-141 is formulated for and administered by intranasal means, and further preferably wherein the PDE-5 inhibitor is administered prior to PT-141.

Abstract: Melanocortin receptor-specific compounds of the general formulas and pharmaceutically acceptable salts thereof, where J is a substituted or unsubstituted monocyclic or bicyclic ring structure, L is a linker, W is a heteroatom unit with at least one cationic center, hydrogen bond donor or hydrogen bond acceptor, Q includes a substituted or unsubstituted aromatic carbocyclic ring, R6, R7, y and z are as defined in the specification, and the carbon atom marked with an asterisk can have any stereochemical configuration, and optionally with one or two additional ring substituents as defined, which compounds bind to one or more melanocortin receptors and are optionally an agonist, a partial agonist, an antagonist, an inverse agonist or an antagonist of an inverse agonist, and may be employed for treatment of one or more melanocortin receptor-associated conditions or disorders, and methods for the use of the compounds of the invention.

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: A method of modulating energy homeostasis in a mammal without eliciting a sexual response by administration of a therapeutically effective amount of a pharmaceutical composition including a melanocortin receptor compound of the formula: where R1 is a bond or a linker unit including from one to six backbone atoms and an unsubstituted naphthalene group, and L, R2, R3 and Rx are as defined in the specification.

Abstract: A thienopyrimidine compound of the formula: wherein R1, R2, R3, and R4 are as defined herein, and methods of use of such compounds for the treatment of melanocortin receptor-associated disorders.

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

Abstract: Compositions and methods are provided for treatment of sexual dysfunction in mammals, including male sexual dysfunction, such as erectile dysfunction, and female sexual dysfunction, wherein pharmaceutically sufficient quantities of a linear or cyclic peptide with a carboxyl terminus —OH group or pharmaceutically acceptable salt thereof and a core His-Phe-Arg-Trp (SEQ ID NO:1) or His-D-Phe-Arg-Trp sequence are administered. Methods of administration include injection, oral, nasal and mucosal administration.

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: A melanocortin receptor-specific compound of the general formula of structure I: 1

Abstract: Compositions and methods are provided for treatment of sexual dysfunction in mammals, including male sexual dysfunction, such as erectile dysfunction, and female sexual dysfunction. In one embodiment, a peptide-based composition including the peptide sequence Ac-Nle-cyclo(-Asp-His-D-Phe-Arg-Trp-Lys)-OH is administered. Methods of administration include injection, oral, nasal and mucosal administration.

Abstract: The invention relates to a method of deriving a peptidomimetic of a biologically active metallopeptide, wherein the peptidomimetic includes at least one non-peptide ring structure defining a template space superimposable on a corresponding defined template space of the metallopeptide, and where the peptidomimetic further includes at least two elements independently including an amino acid residue, amino acid side chain moiety or derivative thereof, the elements defining and occupying a similar descriptor space as corresponding elements of the metallopeptide. The invention further relates to peptidomimetics with a template space heterocyclic ring structure, including 5-, 6- and 8-membered and 5-5- and 6-5-bicyclic fused ring structure melanocortin receptor-specific peptidomimetics.

Abstract: Melanocortin receptor-specific pyrrolidine compounds having the structure: 1

Abstract: Melanocortin receptor-specific piperazine or ketopiperazine compounds having the structure: 1

Abstract: Melanocortin receptor-specific bicyclic compounds having the structure: 1

Abstract: Compositions and methods are provided for treatment of sexual dysfunction in mammals, including male sexual dysfunction, such as erectile dysfunction, and female sexual dysfunction. In one embodiment, a peptide-based composition including the peptide sequence Ac-Nle-cyclo(-Asp-His-D-Phe-Arg-Trp-Lys)-OH is administered. Methods of administration include injection, oral, nasal and mucosal administration.

Abstract: A metallo-construct, which may be a peptide, is provided for use as a biological, therapeutic, diagnostic imaging, or radiotherapeutic agent, and for use in library or combinatorial chemistry methods. The construct has a conformationally constrained global secondary structure obtained upon complexing with a metal ion. The peptide constructs are of the general formula: R1—X—R2 where X is a plurality of amino acids and includes a complexing backbone for complexing metal ions, so that substantially all of the valences of the metal ion are satisfied upon complexation of the metal ion with X, resulting in a specific regional secondary structure forming a part of the global secondary structure; and where R1 and R2 each include from 0 to about 20 amino acids, the amino acids being selected so that upon complexing the metal ion with X at least a portion of either R1 or R2 or both have a structure forming the balance of the conformationally constrained global secondary structure.