A method for refining vasopressin, including: subjecting a crude vasopressin solution to reversed-phase enrichment, reversed-phase salt conversion and reversed-phase purification sequentially using reversed-phase high performance liquid chromatography. The crude vasopressin solution is obtained by oxidizing a crude reduced vasopressin prepared by solid phase synthesis. A super water-resistant packing material is used in the reversed-phase high performance liquid chromatography.

A C-terminus modification to a binding pocket-modified vancomycin introduces a quaternary ammonium salt that provides a binding pocket-modified vancomycin analog with a second mechanism of action that is independent of D-Ala-D-Ala/D-Ala-D-Lac binding. The modification disrupts cell wall integrity and induces cell wall permeability complementary to the glycopeptide inhibition of cell wall synthesis, and provides synergistic improvements in antimicrobial potency (200-fold) against vancomycin-resistant bacteria. Combining the C-terminus and binding pocket modifications with an orthogonal (4-chlorobiphenyl) methyl addition to the vancomycin disaccharide provides even more potent antimicrobial agents whose activity can be attributed to three independent and synergistic mechanisms of action, only one of which requires D-Ala-D-Ala/D-Ala-D-Lac binding. The resulting modified vancomycins display little propensity for acquired resistance through serial exposure of vancomycin-resistant Enterococci and their durability against such challenges as well as their antimicrobial potency follow predicable trends. Methods of treatment with and compositions containing the modified vancomycins are disclosed.

A C-terminus modification to a binding pocket-modified vancomycin introduces a quaternary ammonium salt that provides a binding pocket-modified vancomycin analog with a second mechanism of action that is independent of D-Ala-D-Ala/D-Ala-D-Lac binding. The modification disrupts cell wall integrity and induces cell wall permeability complementary to the glycopeptide inhibition of cell wall synthesis, and provides synergistic improvements in antimicrobial potency (200-fold) against vancomycin-resistant bacteria. Combining the C-terminus and binding pocket modifications with an orthogonal (4-chlorobiphenyl) methyl addition to the vancomycin disaccharide provides even more potent antimicrobial agents whose activity can be attributed to three independent and synergistic mechanisms of action, only one of which requires D-Ala-D-Ala/D-Ala-D-Lac binding. The resulting modified vancomycins display little propensity for acquired resistance through serial exposure of vancomycin-resistant Enterococci and their durability against such challenges as well as their antimicrobial potency follow predicable trends. Methods of treatment with and compositions containing the modified vancomycins are disclosed.

The present invention features peptides, compositions, and related methods for treating gastrointestinal disorders and conditions, including but not limited to, irritable bowel syndrome (IBS), gastrointestinal motility disorders, functional gastrointestinal disorders, gastroesophageal reflux disease (GERD), duodenogastric reflux, Crohn's disease, ulcerative colitis, inflammatory bowel disease, functional heartburn, dyspepsia, visceral pain, gastroparesis, chronic intestinal pseudo-obstruction (or colonic pseudo-obstruction), disorders and conditions associated with constipation, and other conditions and disorders are described herein. using peptides and other agents that activate the guanylate cyclase C (GC-C) receptor.

The present invention features peptides, compositions, and related methods for treating gastrointestinal disorders and conditions, including but not limited to, irritable bowel syndrome (IBS), gastrointestinal motility disorders, functional gastrointestinal disorders, gastroesophageal reflux disease (GERD), duodenogastric reflux, Crohn's disease, ulcerative colitis, inflammatory bowel disease, functional heartburn, dyspepsia, visceral pain, gastroparesis, chronic intestinal pseudo-obstruction (or colonic pseudo-obstruction), disorders and conditions associated with constipation, and other conditions and disorders are described herein. using peptides and other agents that activate the guanylate cyclase C (GC-C) receptor.

Antibodies and antigen-binding fragments thereof that specifically recognize Neurotensin receptor type 1 (NTSR1) are described. These anti-NTSR1 antibodies and antigen-binding fragments thereof, such as single-chain Fv (scFv), are able to inhibit neurotensin-mediated activation of NTSR1 in normal and tumor cells. Methods and uses of antibodies and antigen-binding fragments thereof for treatment of diseases or conditions associated with NTSR1 activity, such as NTSR1-positive cancers or certain metabolic diseases, are also described. Cyclic peptides mimicking the conformation of the second extracellular loop of NTSR1 and capable of inducing the production of anti-NTSR1 antibodies in animals such as chickens are also described.

The present disclosure provides peptoid-based chelating ligands, corresponding cyclic peptoids, and methods of making thereof. Functional groups may be tailored for high metal binding affinity and selectivity. The side chains of a cyclic peptoid according to the present disclosure may be selected based on, for example, high affinity for actinide or other metal ions, selectivity for actinide or other metal ions, the ability to recover a metal once it is bound to the peptoid, and whether the overall peptoid should be hydrophobic or hydrophilic. Unlike siderophores, peptoid-based chelating ligands of the present disclosure are not readily hydrolyzed under physiological conditions. Therefore, peptoid-based chelating ligands may be, for example, used to treat actinide (e.g., iron and lead) poisoning in vivo. Moreover, peptoid-based chelating ligands of the present disclosure may be used for medical imaging, chelation therapy, drug delivery, and separation technologies, for example.

The present disclosure provides peptoid-based chelating ligands, corresponding cyclic peptoids, and methods of making thereof. Functional groups may be tailored for high metal binding affinity and selectivity. The side chains of a cyclic peptoid according to the present disclosure may be selected based on, for example, high affinity for actinide or other metal ions, selectivity for actinide or other metal ions, the ability to recover a metal once it is bound to the peptoid, and whether the overall peptoid should be hydrophobic or hydrophilic. Unlike siderophores, peptoid-based chelating ligands of the present disclosure are not readily hydrolyzed under physiological conditions. Therefore, peptoid-based chelating ligands may be, for example, used to treat actinide (e.g., iron and lead) poisoning in vivo. Moreover, peptoid-based chelating ligands of the present disclosure may be used for medical imaging, chelation therapy, drug delivery, and separation technologies, for example.

The invention provides an improved method of macrocyclization of peptidomimetics, as measured by isolated yields and product distribution, which comprises substitution of one or more of the backbone amide CO bonds with a turn-inducing motif. The method is general with enhancements seen across a range of ring sizes (e.g. tri-, tetra-, penta- and hexapeptides). Specifically, the invention provides a peptidomimetic macrocycle comprising a carbonylbioisosteric turn-inducing element having the structure: (I) wherein X is a heteroatom; and wherein R.sub.1 to R.sub.6 are each independently selected from alkyl, aryl, heteroaryl and H.

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The invention provides an improved method of macrocyclization of peptidomimetics, as measured by isolated yields and product distribution, which comprises substitution of one or more of the backbone amide CO bonds with a turn-inducing motif. The method is general with enhancements seen across a range of ring sizes (e.g. tri-, tetra-, penta- and hexapeptides). Specifically, the invention provides a peptidomimetic macrocycle comprising a carbonylbioisosteric turn-inducing element having the structure: (I) wherein X is a heteroatom; and wherein R.sub.1 to R.sub.6 are each independently selected from alkyl, aryl, heteroaryl and H.

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