Peptide analogs of θ-defensins have been developed that are effective in treating multi-drug resistant microbial infections when used at concentrations below those needed to provide a microbicidal effect. These peptides were found to modulate host defense mechanisms to increase clearance of microbial pathogens, enhance phagocytic activity, and enhance neutrophil recruitment while reducing inflammation.

The present invention relates to a polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the bicyclic peptides of the invention are conjugated to a carrier peptide in order to greatly enhance the bacterial cell killing activity. More particularly, the invention describes peptides which are high affinity binders of penicillin-binding proteins (PBPs), such as PBP3 and PBP3a. The invention also includes pharmaceutical compositions comprising said conjugates and to the use of said conjugates in suppressing or treating a disease or disorder mediated by bacterial infection or for providing prophylaxis to a subject at risk of infection.

The present invention relates to a polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the bicyclic peptides of the invention are conjugated to a carrier peptide in order to greatly enhance the bacterial cell killing activity. More particularly, the invention describes peptides which are high affinity binders of penicillin-binding proteins (PBPs), such as PBP3 and PBP3a. The invention also includes pharmaceutical compositions comprising said conjugates and to the use of said conjugates in suppressing or treating a disease or disorder mediated by bacterial infection or for providing prophylaxis to a subject at risk of infection.

A method for preparing a cyclopeptide and a cyclopeptide preparing by the method are disclosed. The method includes the following steps: (A) providing compounds represented by the following formulas (I-1) and (I-2): ##STR00001## wherein, G, R.sub.a, R.sub.b, R.sub.c, R.sub.d, and R.sub.e are defined in the specification; (B) performing a reaction between the compounds of formulas (I-1) and (I-2) to obtain a compound represented by the following formula (I-3): ##STR00002##
and (C) performing a cyclization reaction of the compound of formula (I-3) with a catalyst of formula (II) and deprotection to obtain a compound represented by the following formula (III): ##STR00003## wherein, G′, Q, M, L.sup.1, L.sup.2, m, y, and z are defined in the specification.

A method for preparing a cyclopeptide and a cyclopeptide preparing by the method are disclosed. The method includes the following steps: (A) providing compounds represented by the following formulas (I-1) and (I-2): ##STR00001## wherein, G, R.sub.a, R.sub.b, R.sub.c, R.sub.d, and R.sub.e are defined in the specification; (B) performing a reaction between the compounds of formulas (I-1) and (I-2) to obtain a compound represented by the following formula (I-3): ##STR00002##
and (C) performing a cyclization reaction of the compound of formula (I-3) with a catalyst of formula (II) and deprotection to obtain a compound represented by the following formula (III): ##STR00003## wherein, G′, Q, M, L.sup.1, L.sup.2, m, y, and z are defined in the specification.

The present invention relates to peptide ligands of the melanocortin receptors, in particular the melancortin-4 receptor, and as such, are useful in the treatment of disorders responsive to the activation of this receptor, such as insulin resistance.

The present invention relates to peptide ligands of the melanocortin receptors, in particular the melancortin-4 receptor, and as such, are useful in the treatment of disorders responsive to the activation of this receptor, such as insulin resistance.

The disclosure is directed to compounds and methods for preparing purified macrocyclic peptide using “catch-release” methods. These methods comprise reacting a free amino group of a resin-bound linear peptide with an azide- or alkyne-functionalized cap to form a resin-bound capped linear peptide having an azide- or alkyne-functionalized cap; cleaving the capped linear peptide from the resin to form a free capped linear peptide having an azide- or alkyne-functionalized cap; reacting the free capped linear peptide having an azide-functionalized cap with an alkyne-functionalized catch resin, or reacting the free capped linear peptide having an akynyl-functionalized cap with an azide functionalized catch resin, to form a catch-resin bound capped linear peptide; reacting the catch-resin bound capped linear peptide under conditions sufficient to effect macrocyclization of the linear peptide and release of the macrocyclic peptide from the catch resin.

The disclosure is directed to compounds and methods for preparing purified macrocyclic peptide using “catch-release” methods. These methods comprise reacting a free amino group of a resin-bound linear peptide with an azide- or alkyne-functionalized cap to form a resin-bound capped linear peptide having an azide- or alkyne-functionalized cap; cleaving the capped linear peptide from the resin to form a free capped linear peptide having an azide- or alkyne-functionalized cap; reacting the free capped linear peptide having an azide-functionalized cap with an alkyne-functionalized catch resin, or reacting the free capped linear peptide having an akynyl-functionalized cap with an azide functionalized catch resin, to form a catch-resin bound capped linear peptide; reacting the catch-resin bound capped linear peptide under conditions sufficient to effect macrocyclization of the linear peptide and release of the macrocyclic peptide from the catch resin.

A compound of the Formula (I) is disclosed:

##STR00001##

or pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification. Also described are a pharmaceutical composition comprising the same and a method for treating or preventing viral infections, inflammation, dry eye, central nervous disorders, cardiovascular diseases, cancer, obesity, diabetes, muscular dystrophy, lung, and liver, and kidney diseases, and hair loss using the same.