Abstract: The invention provides isolated agents having a core peptide selected from the group consisting of Core peptides 5 through 39 and 42 through 55, wherein the agent derepresses an IAP-inhibited caspase. Also provided is an isolated agent having a core structure selected from any of the structures shown in FIGS. 5, 9, 10, 14B, 21-24 and 48, a core structure selected from the group of TPI 759, TPI 882, TPI 914 or TPI 927; and a core structure from a library selected from TPI 1391, TPI 1349, TPI 1396, TPI 1509, TPI 1540, TPI 1400, TPI 792, TPI 1332, TPI 1567, TPI 1576 and TPI 1577, wherein the agent derepresses an IAP-inhibited caspase. The invention further provides a method of derepressing an IAP-inhibited caspase.

Abstract: Small, polybasic peptides are disclosed that are effective as furin inhibitors, e.g. hexa- to nona-peptides having L-Arg or L-Lys in most positions. Removing the peptide terminating groups can improve inhibition of furin. High inhibition was seen in a series of non-amidated and non-acetylated polyarginines. The most potent inhibitor identified to date, nona-L-arginine, had a Ki against furin of 40 nM. Non-acetylated, poly-D-arginine-derived molecules are preferred furin inhibitors for therapeutic uses, such as inhibiting certain bacterial infections, viral infections, and cancers. Due to their relatively small size, these peptides should be non-immunogenic. These peptides are efficiently transported across cell membranes.

Abstract: A solid phase synthetic method is disclosed in which the usual solid phase synthetic steps are carried out and the spent solid phase support is reacted to form a volatilizable compound upon cleavage of the reaction product from the solid phase support. The cleaved product is then separated from the volatile compound by volatilization of that compound. Exemplary solid supports that form a volatilizable compound are also disclosed.

Abstract: The invention provides isolated agents having novel chemical structures and possessing superior activity as derepressors of IAP inhibited caspase. The invention further provides a method of derepressing an IAP-inhibited caspase. The invention further provides assay methods employing labeled compounds of the invention, especially fluorescent labeled compounds.

Abstract: A solid phase synthetic method is disclosed in which the usual solid phase synthetic steps are carried out and the spent solid phase support is reacted to form a volatilizable compound upon cleavage of the reaction product from the solid phase support. The cleaved product is then separated from the volatile compound by volatilization of that compound. Exemplary solid supports that form a volatilizable compound are also disclosed.

Abstract: Membrane translation peptides, compositions comprising them, chimeric molecules comprising them, and methods of using them to achieve transmembrane transport of various agents.

Abstract: Small, polybasic peptides are disclosed that are effective as furin inhibitors, e.g. hexa- to nona-peptides having L-Arg or L-Lys in most positions. Removing the peptide terminating groups can improve inhibition of furin. High inhibition was seen in a series of non-amidated and non-acetylated polyarginines. The most potent inhibitor identified to date, nona-L-arginine, had a Ki against furin of 40 nM. Non-acetylated, poly-D-arginine-derived molecules are preferred furin inhibitors for therapeutic uses, such as inhibiting certain bacterial infections, viral infections, and cancers. Due to their relatively small size, these peptides should be non-immunogenic. These peptides are efficiently transported across cell membranes.

Abstract: Neuroprotectant agents are provided which do not contain peptides and axe protected from the degradation that limits the use of peptide-based drugs in systemic circulation. With great selectivity for NMDA receptors, the agents exert an open channel block on NMDA receptors, and protect neuronal cells containing such receptors from excitatoxic cell death.

Abstract: A method of synthesis on a solid phase support is disclosed that provides a cleaved product containing a protecting group that would have been cleaved by reaction with anhydrous HF wherein the support is volatilized during cleavage of the protected product from the support by reaction with diluted HF.

Abstract: The invention provides isolated agents having a core peptide selected from the group consisting of Core peptides 5 through 39 and 42 through 55, wherein the agent derepresses an IAP-inhibited caspase. Also provided is an isolated agent having a core structure selected from any of the structures shown in FIGS. 5, 9, 10, 14B, and 21-24 wherein said agent derepresses an IAP-inhibited caspase. The invention further provides a method of derepressing an IAP-inhibited caspase. The method consists of contacting an IAP-inhibited caspase with an effective amount of an agent to derepress an IAP-inhibited caspase, the agent having a core motif selected from the group consisting of a core peptide having a sequence set forth in any of Core peptides 4 through 39 and 42 through 55, and a core structure selected from the group consisting of TPI759, TPI882, TPI914 or TPI927.

Abstract: The invention provides isolated agents having a core peptide selected from the group consisting of Core peptides 5 through 39 and 42 through 55, wherein the agent derepresses an IAP-inhibited caspase. Also provided is an isolated agent having a core structure selected from any of the structures shown in FIGS. 5, 9, 10, 14B, and 21-24 wherein said agent derepresses an IAP-inhibited caspase. The invention further provides a method of derepressing an IAP-inhibited caspase. The method consists of contacting an IAP-inhibited caspase with an effective amount of an agent to derepress an IAP-inhibited caspase, the agent having a core motif selected from the group consisting of a core peptide having a sequence set forth in any of Core peptides 4 through 39 and 42 through 55, and a core structure selected from the group consisting of TPI759, TPI882, TPI914 or TPI927.

Abstract: The invention provides isolated agents having a core peptide selected from the group consisting of Core peptides 5 through 39 and 42 through 55, wherein the agent derepresses an IAP-inhibited caspase. Also provided is an isolated agent having a core structure selected from any of the structures shown in FIGS. 5, 9, 10, 14B, and 21-24, a core structure selected from the group of TPI 759, TPI 882, TPI 914 or TPI 927; and a core structure from a library selected from TPI 1391, TPI 1349, TPI 1396, TPI 1509, TPI 1540, TPI 1400, TPI 792 and TPI 1332, wherein the agent derepresses an IAP-inhibited caspase. The invention further provides a method of derepressing an IAP-inhibited caspase.

Abstract: The synthesis of individual di- and tri-substituted-1,4-diazacyclic compounds having 6- to 8-atoms in the cyclic ring, their corresponding 1,6-diketo-2,5-diazacyclic compounds and similar 1,4-diazacyclic ring compounds having one ring carbonyl gorup and 6-8 atoms in the ring is disclosed, as are libraries of such compounds. Methods of preparing and using the libraries of compounds as well as individual compounds of the libraries are also disclosed.

Abstract: Membrane translocation peptides, compositions comprising them, chimeric molecules comprising them, and methods of using them to achieve transmembrane transport of various agents.

Abstract: The solid-phase synthesis of individual 1,3-disubstituted and 1,3,5-trisubstituted-1,3,5-triazine-2,4,6-triones and libraries thereof from a resin is described. Reaction of resin-bound amino acids with isocyanates yields resin-bound ureas, which further react with chlorocarbonyl isocyanate to selectively afford the resin-bound 1,3-disubstituted-1,3,5-triazine-2,4,6-triones. Selective alkylation at the N-5 position of the resin-bound 1,3-disubstituted-1,3,5-triazine-2,4,6-triones produces a trisubstituted triazinetrione. The products are cleaved from their solid support and obtained in good yield and purity.

Abstract: The synthesis of individual di- and tri-substituted-1,4-diazacyclic compounds having 6- to 8-atoms in the cyclic ring, their corresponding 1,6-diketo-2,5-diazacyclic compounds and similar 1,4-diazacyclic ring compounds having one ring carbonyl gorup and 6-8 atoms in the ring is disclosed, as are libraries of such compounds. Methods of preparing and using the libraries of compounds as well as individual compounds of the libraries are also disclosed.

Abstract: UEA-1 Mimetics, pharmaceutical formulations comprising them, and their uses as targeting agents for therapeutic and diagnostic purposes.

Abstract: Neuroprotectant agents are provided which do not contain peptides and are protected from the degradation that limits the use of peptide-based drugs in systemic circulation. With great selectivity for NMDA receptors, the agents exert an open channel block on NMDA receptors, and protect neuronal cells containing such receptors from excitotoxic cell death.

Abstract: Individual substituted [3,5,7]-1H-imidazo[1,5-a]imidazol-2(3H)-one compounds and their pharmaceutically-acceptable salts are disclosed, as are libraries of such compounds. Methods of preparing and using the libraries of compounds as well as individual compounds of the libraries are also disclosed.

Abstract: The solid-phase synthesis of individual 1,3-disubstituted and 1,3,5-trisubstituted-1,3,5-triazine-2,4,6-triones and libraries thereof from a resin is described. Reaction of resin-bound amino acids with isocyanates yields resin-bound ureas, which further react with chlorocarbonyl isocyanate to selectively afford the resin-bound 1,3-disubstituted-1,3,5-triazine-2,4,6-triones. Selective alkylation at the N-5 position of the resin-bound 1,3-disubstituted-1,3,5-triazine-2,4,6-triones produces a trisubstituted triazinetrione. The products are cleaved from their solid support and obtained in good yield and purity.