Abstract: The present invention relates to inhibitors of post-proline cleaving enzyme, such as inhibitors of dipeptidyl peptidase IV, as well as pharmaceutical compositions thereof, and methods for using such inhibitors. In particular, the inhibitors of the present invention incorporate a lactam ring in the backbone of the inhibitors. The compounds of the present invention can have a better therapeutic index, owing in part to reduced toxicity and/or improved specificity for the target protease.

Abstract: The present invention relates to inhibitors of lipases, such as inhibitors of endothelial lipase, as well as pharmaceutical compositions thereof, and methods for using such inhibitors. The prototype of these inhibitors has lipophilic portion and an electrophilic site.

Abstract: The invention provides compounds and methods for inhibiting proteases. One aspect of the invention features pro-soft inhibitors which react with an activating protease to release an active inhibitor moiety in proximity to a target protease. In certain instances, compounds inhibit proteasomes and/or post-proline cleaving enzymes (PPCE), such as dipeptidyl peptidase IV. The compounds of the invention provide a better therapeutic index, owing in part to reduced toxicity and/or improved specificity for the targeted protease.

Abstract: The present invention relates to inhibitors of post-proline cleaving enzymes, such as inhibitors of dipeptidyl peptidase IV, as well as pharmaceutical compositions thereof, and methods for using such inhibitors. In particular, the inhibitors of the present invention are improved over those in the prior art by selection of particular classes of sidechains in the P1 and/or P2 position of the inhibitor that contain a carboxylic acid moiety. The compounds of the present invention can have a better therapeutic index, owing in part to reduced toxicity and/or improved specificity for the targeted protease.

Abstract: The present invention relates to compositions of peptide and polypeptide analogs that are resistant to proteolysis, pharmaceutical uses thereof, and methods of preparation thereof.

Abstract: The present invention relates to compositions of peptide and polypeptide analogs that are resistant to proteolysis, pharmaceutical uses thereof, and methods of preparation thereof.

Abstract: The present invention relates to inhibitors of post-proline cleaving enzymes, such as inhibitors of dipeptidyl peptidase IV, as well as pharmaceutical compositions thereof, and methods for using such inhibitors. In particular, the inhibitors of the present invention are improved over those in the prior art by selection of particular classes of sidechains in the P1 and/or P2 position of the inhibitor that contain a carboxylic acid moiety. The compounds of the present invention can have a better therapeutic index, owing in part to reduced toxicity and/or improved specificity for the targeted protease.

Abstract: The present invention relates to compositions of peptide and polypeptide analogs that are resistant to proteolysis, pharmaceutical uses thereof, and methods of preparation thereof.

Abstract: The invention provides methods for rapidly determining kinase binding site motifs using a oriented degenerate peptide library approach. The methods involve the selection of peptides by binding affinity. Inhibitors of kinases that include or compete for the binding site motifs determined using the methods also are provided, as are methods and compositions for using these binding site motifs and inhibitors.

Abstract: Methods for determining an optimal binding motif for a binding compound are provided in which the binding compound is contacted with an oriented degenerate cyclic peptide library (ODCPL) under conditions which allow for interaction between the binding compound and the ODCPL such that a complex is formed between the binding compound and a subpopulation of library members capable of interacting with the binding compound. The subpopulation of library members capable of interacting with the binding compound is then separated from library members that are incapable of interacting with the binding compound. The subpopulation of library members capable of interacting with the binding compound is linearized to form a subpopulation of linearized library members.

Abstract: Disclosed are methods of purifying and analyzing cyclic peptide libraries using hydrophobic-hydrophobic interaction. An embodiment of the invention includes associating a hydrophobic tag, e.g., a fluorenylmethoxycarbonyl group (Fmoc), with non-cyclized linear peptide contaminants, followed by separation of the cyclic peptide library from the tagged linear peptide contaminants using a hydrophobic support such as a reversed phase chromatography column. Consequently, the cyclic peptide library is separated from the linear peptide contaminants since the linear peptide contaminants elute later from the support. Another aspect of the invention is directed to the analysis of the proportion of linear peptide contaminants in a cyclic peptide library. Also included within the scope of the invention are the compositions of matter which result from practicing methods of the invention.