Abstract: Non-natural oligomers have recently shown promise as functional analogs of lung surfactant proteins B and C (SP-B and SP-C), two helical and amphiphilic proteins that are critical for normal respiration. The generation of non-natural mimics of SP-B and SP-C has previously been restricted to step-by-step, sequence-specific synthesis, which results in discrete oligomers that are intended to manifest specific structural attributes. Presented herein an alternative approach to SP-B mimicry that is based on sequence-random copolymers containing cationic and lipophilic subunits. These materials, members of the nylon-3 family, are prepared by ring-opening polymerization of ?-lactams. The best of the nylon-3 polymers display promising in vitro surfactant activities in a mixed lipid film. Pulsating bubble surfactometry data indicate that films containing the most surface-active polymers attain adsorptive and dynamic-cycling properties that surpass those of discrete peptides intended to mimic SP-B.

Abstract: Described herein are peptide analogs of glucagon-like peptide 1 (GLP-1) that retain agonist activity, but are more resistant to proteolytic degradation than native GLP-1. In the analogs, at least one ?-amino acid found in the native GLP-1 is replaced with a ?-amino acid residue, which may or may not be cyclically constrained. Pharmaceutical compositions containing the analogs are described, as are methods to treat diabetes, and methods to make proteolytically resistant GLP-1 analogs.

Abstract: This invention relates to novel compositions comprising analogs of naturally occurring polypeptides, wherein the analog comprises an ?-amino acid and at least one ?-amino acid. Administration of the compositions may be used for effecting treatment or prevention of a plurality of disease states caused by dysfunctional biochemical or biological pathways. The compositions and methods of this invention are particularly useful to identify novel therapeutic modulators of in-vivo receptor activity with extended half-lives and relevant bioactivity as compared to the naturally translated polypeptides upon which the analogs are derived.

Abstract: This invention relates to novel compositions comprising analogs of glucagon, wherein the analog comprises an ?-amino acid and at least one ?-amino acid. Administration of the compositions may be used for effecting treatment or prevention of a plurality of disease states caused by dysfunctional biochemical or biological pathways, including diabetes and other metabolic disorders. The compositions and methods of this invention are particularly useful to identify novel therapeutic modulators of in-vivo receptor activity with extended half-lives and relevant bioactivity as compared to the naturally translated polypeptides upon which the analogs are derived.

Abstract: This invention relates to novel compositions comprising analogs of naturally occurring polypeptides, wherein the analog comprises an ?-amino acid and at least one ?-amino acid. Administration of the compositions may be used for effecting treatment or prevention of a plurality of disease states caused by dysfunctional biochemical or biological pathways. The compositions and methods of this invention are particularly useful to identify novel therapeutic modulators of in-vivo receptor activity with extended half-lives and relevant bioactivity as compared to the naturally translated polypeptides upon which the analogs are derived.

Abstract: Disclosed is a method of making ?-polypeptides. The method includes polymerizing ?-lactam-containing monomers in the presence of a base initiator and a co-initiator which is not a metal-containing molecule to yield the product ?-polypeptides. Specifically disclosed are methods wherein the base initiator is potassium t-butoxide, lithium bis(trimethylsilyl)amide (LiN(TMS)2), potassium bis(trimethyl-silyl)amide, and sodium ethoxide, and the reaction is carried out in a solvent such as chloroform, dichloromethane, dimethylsulfoxide, or tetrahydrofuran.

Abstract: Described herein are peptide analogs of glucagon-like peptide 1 (GLP-1) that retain agonist activity, but are more resistant to proteolytic degradation than native GLP-1. In the analogs, at least one ?-amino acid found in the native GLP-1 is replaced with a ?-amino acid residue, which may or may not be cyclically constrained. Pharmaceutical compositions containing the analogs are described, as are methods to treat diabetes, and methods to make proteolytically resistant GLP-1 analogs.

Abstract: Disclosed is a method of making ?-polypeptides. The method includes polymerizing ?-lactam-containing monomers in the presence of a base initiator and a co-initiator which is not a metal-containing molecule to yield the product ?-polypeptides. Specifically disclosed are methods wherein the base initiator is potassium t-butoxide, lithium bis(trimethylsilyl)amide (LiN(TMS)2), potassium bis(trimethyl-silyl)amide, and sodium ethoxide, and the reaction is carried out in a solvent such as chloroform, dichloromethane, dimethylsulfoxide, or tetrahydrofuran.

Abstract: A method and corresponding composition to inhibit outgrowth of C. difficile spores and/or to inhibit growth of C. difficile vegetative cells in a mammal in which an amount of a nylon-3 polymer or nylon-3 copolymer or a pharmaceutically suitable salt thereof is administered to the subject.

Abstract: Described is a method of fabricating biologically active, unnatural polypeptides. The method includes the steps of selecting a biologically active polypeptide or biologically active fragment thereof having an amino acid sequence comprising ?-amino acid residues, and fabricating a synthetic polypeptide that has an amino acid sequence that corresponds to the sequence of the biologically active polypeptide, but wherein about 14% to about 50% of the ?-amino acid residues found in the biologically active polypeptide or fragment of step (a) are replaced with ?-amino acid residues, and the ?-amino acid residues are distributed in a repeating pattern.

Abstract: Pharmaceutical compositions containing biocidal co-polymers of poly(styrenes), poly(acrylates), poly(acrylamides), and poly(C1-C6)alkylene glycols are disclosed, along with methods of using the compositions to treat microbial infections in mammals.

Abstract: Described are ?/?-peptide mimics of Z-domain scaffold peptides, methods of making them, and methods of using them. The ?/?-peptide mimics include ?-amino acid residues and, optionally, disulfide bonds to stabilize the conformation of the mimics. The compounds may be truncated as compared to conventional Z-domain scaffold peptides and are resistant to proteolytic degradation due to the presence of ?-amino acid residues. The mimics can be made so as to bind selectively to a desired target.

Abstract: This invention relates to novel compositions comprising analogs of naturally occurring polypeptides, wherein the analog comprises an ?-amino acid and at least one ?-amino acid. Administration of the compositions may be used for effecting treatment or prevention of a plurality of disease states caused by dysfunctional biochemical or biological pathways. The compositions and methods of this invention are particularly useful to identify novel therapeutic modulators of in-vivo receptor activity with extended half-lives and relevant bioactivity as compared to the naturally translated polypeptides upon which the analogs are derived.

Abstract: Disclosed is a method of making ?-polypeptides. The method includes polymerizing ?-lactam-containing monomers in the presence of a base initiator and a co-initiator which is not a metal-containing molecule to yield the product ?-polypeptides. Specifically disclosed are methods wherein the base initiator is potassium t-butoxide, lithium bis(trimethylsilyl)amide (LiN(TMS)2), potassium bis(trimethyl-silyl)amide, and sodium ethoxide, and the reaction is carried out in a solvent such as chloroform, dichloromethane, dimethylsulfoxide, or tetrahydrofuran.

Abstract: The present invention is directed to the design, synthesis and use of various ?-peptides exhibiting antifungal activity. The ?-peptides are relatively short in length, adopt globally amphiphilic conformations, and cause little lysis of human red blood cells at concentrations that kill Candida albicans, a common human fungal pathogen.

Abstract: Disclosed is a method of making ?-polypeptides. The method includes polymerizing ?-lactam-containing monomers in the presence of a base initiator and a co-initiator which is not a metal-containing molecule to yield the product ?-polypeptides. Specifically disclosed are methods wherein the base initiator is potassium t-butoxide, lithium bis(trimethylsilyl)amide (LiN(TMS)2), potassium bis(trimethyl-silyl)amide, and sodium ethoxide, and the reaction is carried out in a solvent such as chloroform, dichloromethane, dimethylsulfoxide, or tetrahydrofuran.

Abstract: Non-natural oligomers have recently shown promise as functional analogues of lung surfactant proteins B and C (SP-B and SP-C), two helical and amphiphilic proteins that are critical for normal respiration. The generation of non-natural mimics of SP-B and SP-C has previously been restricted to step-by-step, sequence-specific synthesis, which results in discrete oligomers that are intended to manifest specific structural attributes. Presented herein an alternative approach to SP-B mimicry that is based on sequence-random copolymers containing cationic and lipophilic subunits. These materials, members of the nylon-3 family, are prepared by ring-opening polymerization of ?-lactams. The best of the nylon-3 polymers display promising in vitro surfactant activities in a mixed lipid film. Pulsating bubble surfactometry data indicate that films containing the most surface-active polymers attain adsorptive and dynamic-cycling properties that surpass those of discrete peptides intended to mimic SP-B.

Abstract: Pharmaceutical compositions containing biocidal co-polymers of poly(styrenes), poly(acrylates), poly(acrylamides), and poly(C1-C6)alkylene glycols are disclosed, along with methods of using the compositions to treat microbial infections in mammals.

Abstract: Described are ?/?-peptide mimics of Z-domain scaffold peptides, methods of making them, and methods of using them. The ?/?-peptide mimics include ?-amino acid residues and, optionally, disulfide bonds to stabilize the conformation of the mimics. The compounds may be truncated as compared to conventional Z-domain scaffold peptides and are resistant to proteolytic degradation due to the presence of ?-amino acid residues. The mimics can be made so as to bind selectively to a desired target.

Abstract: Non-natural oligomers have recently shown promise as functional analogues of lung surfactant proteins Band C (SP-B and SP-C), two helical and amphiphilic proteins that are clitical for normal respiration. The generation of non-natural mimics of SP-B and SP-C has previously been restlicted to step-by-step, sequence-specific synthesis, which results in discrete oligomers that are intended to manifest specific structural attributes. Presented herein an alternative approach to SP-R mimicry that is based on sequence-random copolymers containing cationic and lipophilic subunits. These materials, members of the nylon-3 family, arc prepared by ling-opening polymelization of 13-lactams. The best of the nylon-3 polymers display promising in vitro surfactant activities in a mixed lipid film. Pulsating bubble surfactometry data indicate that films containing the most surface-active polymers attain adsorptive and dynamic-cycling properties that surpass those of discrete peptides intended to mimic SP-B.