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: 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: 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: Described are polypeptide analogs of parathyroid hormone (PTH) that include at least two non-adjacent ?-amino acid residues in place of a naturally occurring ?-amino acid residues. Also described are pharmaceutical compositions useful for treating hypoparathyroidism that contain the analogs and methods of using the analogs to treat hypoparathyroidism.

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: Disclosed are ?-amino acid monomers containing cylcoalkyl, cycloalkenyl, and heterocylic substituents which encompass the ? and ? carbons of the peptide backbone and ?-polypeptides made from such monomers. Method of generating combinatorial libraries of polypeptides containing the ?-peptide residues and libraries formed thereby are disclosed.

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: 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: 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: Disclosed are ?-amino acid monomers containing cylcoalkyl, cycloalkenyl, and heterocylic substituents which encompass the ? and ? carbons of the peptide backbone and ?-polypeptides made from such monomers. Method of generating combinatorial libraries of polypeptides containing the ?-peptide residues and libraries formed thereby are disclosed.

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.

Abstract: Disclosed are isolated, unnatural polypeptides containing cyclically-constrained ?-amino acid residues and cyclically-constrained ?-amino acid residues. The compounds are unnatural and because they contain rotationally constrained residues that are not amenable to enzymatic degradation, the compounds are useful to probe protein-protein and other large molecule interactions.

Abstract: The invention provides methods and reagents for the metathesis of secondary amides via a transacylation mechanism employing catalytic quantities of an imide initiator and a Brønsted base. Equilibrium-controlled exchange between various amide reactant pairs is demonstrated for substrates bearing a variety of N-alkyl and N-aryl substituents.

Abstract: The present invention provides materials and methods that make liquid crystal phases accessible with relatively short ?-peptides in aqueous solvents.

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: 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: Disclosed are isolated, unnatural polypeptides containing cyclically-constrained ?-amino acid residues and cyclically-constrained ?-amino acid residues. The compounds are unnatural and because they contain rotationally constrained residues that are not amenable to enzymatic degradation, the compounds are useful to probe protein-protein and other large molecule interactions.

Abstract: The present invention provides a method for the synthesis of ?2-amino acids. The method also provides methods yielding ?-substituted ?-amino aldehydes and ?-substituted ?-amino alcohols. The present method according to this invention allows for increased yield and easier purification using minimal chromatography or crystallization. The methods described herein are based on an aldehyde aminomethylation which involves a Mannich reaction between an aldehyde and a formaldehyde-derived N,O-acetal (iminium precursor) and a catalyst, such as, for example, L-proline or a pyrrolidine. The invention allows for large scale, commercial preparation of ?2-amino acids.

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 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.