Abstract: The present invention provides, in part, compositions comprising a peptide that is larazotide or larazotide derivative, or salt thereof, contained within a matrix that provides for controlled release and sustained release formulations. The present invention contemplates that these compositions, formulations and methods can be useful for treating diseases and disorders of the small bowel.

Abstract: The invention provides methods and compositions for treatment of pain, such as joint pain, using capsaicin in a procedure that attenuates transient burning sensation experienced by patients due to capsaicin administration. The methods desirably provide relief from joint pain, such as osteoarthritic knee joint pain, for an extended duration, such as at least about 3 months, 6 months, 9 months, or 1 year. To attenuate the adverse side effect of a transient burning sensation caused by capsaicin-induced neuronal excitation, the methods utilize a cooling article, such as a material wrap cooled via a circulating fluid, to reduce the temperature of tissue to be exposed to capsaicin to within a certain range for certain durations of time, optionally in combination with administering a local anesthetic agent, resulting in the substantial reduction or even elimination of transient burning sensation caused by capsaicin.

Abstract: Compounds that modulate natural ? amyloid peptide aggregation are provided. The modulators of the invention comprise a peptide, preferably based on a ? amyloid peptide, that is comprised entirely of D-amino acids. Preferably, the peptide comprises 3–5 D-amino acid residues and includes at least two D-amino acid residues independently selected from the group consisting of D-leucine, D-phenylalanine and D-valine. In a particularly preferred embodiment, the peptide is a retro-inverso isomer of a ? amyloid peptide, preferably a retro-inverso isomer of A?17-21. In certain embodiments, the peptide is modified at the amino-terminus, the carboxy-terminus, or both. Preferred amino-terminal modifying groups include cyclic, heterocyclic, polycyclic and branched alkyl groups. Preferred carboxy-terminal modifying groups include an amide group, an alkyl amide group, an aryl amide group or a hydroxy group.

Abstract: Peptides called receptor mediated permeabilizers (RMP) increase the permeability of the blood-brain barrier to molecules such as therapeutic agents or diagnostic agents. The permeabilizer A-7 or conformational analogues can be intravenously co-administered to a host together with molecules whose desired destination is the interstitial fluid compartment of the brain. Alternatively, the permeabilizer A-7 or conformational analogues can be administered sequentially with the molecule(s) of interest and these molecules can also be administered by routes other than intravascular. The permeabilizer A-7 or conformational analogues allow these molecules to penetrate the blood-brain barrier and arrive in the interstitial fluid.

Abstract: Polypeptides called receptor mediated permeabilizers (RMP) increase the permeability of the blood-brain barrier to molecules such as therapeutic agents or diagnostic agents. These receptor mediated permeabilizers are more efficacious than bradykinin in causing the blood-brain barrier to become more permeable. The permeabilizer A-7 or conformational analogues can be intravenously co-administered to a host together with molecules whose desired destination is the cerebrospinal fluid compartment of the brain. The permeabilizer A-7 or conformational analogues allow these molecules to penetrate the blood-brain barrier and arrive at this destination.

Abstract: Polypeptides called receptor mediated permeabilizers (RMP) increase the permeability of the blood-brain barrier to molecules such as therapeutic agents or diagnostic agents. These receptor mediated permeabilizers are more efficacious than bradykinin in causing the blood-brain barrier to become more permeable. The permeabilizer A-7 or conformational analogues can be intravenously co-administered to a host together with molecules whose desired destination is the cerebrospinal fluid compartment of the brain. The permeabilizer A-7 or conformational analogues allow these molecules to penetrate the blood-brain barrier and arrive at this destination.

Abstract: Nucleic acid hybridization probes are provided which comprise an N.sup.4 -(substituted amino)cytosine moiety, wherein the substituted amino group comprises a tag moiety, whereby the probe is detected. Methods of preparing probes of the invention, intermediates used in such methods, and methods of using the probes of the invention in hybridization assays are also provided. Typical tag moieties employed with the probes of the invention are biotinyl, aminothiadiazole and fluorescein derivatives, connected to N.sup.4 -amino groups of modified cytosines of the probe through linker moieties. Probes tagged with biotin are typically detected by binding to the biotinyl moieties, through a streptavidin or avidin molecule, a reporter group which includes streptavidin or avidin and then detecting a signal due to the reporter group.

Abstract: Fluorescent linker moieties are provided which comprise a fluorescent compound such as fluorescein attached to a linker moiety such that a functional group of the linker is available for attachment to an affinity molecule such as a nucleic acid which has an N.sup.4 (substituted amino) cytosine moiety. Probes tagged with fluorescent derivatives such as fluorescein, tetramethyrhodamine or tetraethylrhodamine may be detected by fluorescence spectroscopic methods.

Abstract: Novel, biologically active, 28-amino acid analogs of human vasoactive intestinal peptide are provided.

Abstract: Novel biologically active vasoactive intestinal peptide (VIP) analogues are provided.

Abstract: Nucleic acid hybridization probes are provided which comprise an N.sup.4 -(substituted amino)cytosine moiety, wherein the substituted amino group comprises a tag moiety, whereby the probe is detected. Methods of preparing probes of the invention, intermediates used in such methods, and methods of using the probes of the invention in hybridization assays are also provided. Typical tag moieties employed with the probes of the invention are biotinyl, aminothiadiazole and fluorescein derivatives, connected to N.sup.4 -amino groups of modified cytosines of the probe through linker moieties. Probes tagged with biotin are typically detected by binding to the biotinyl moieties, through a streptavidin or avidin molecule, a reporter group which includes streptavidin or avidin and then detecting a signal due to the reporter group.

Abstract: Nucleic acid hybridization probes are provided which comprise nucleoside bases or terminal nucleotide phosphates chemically linked to aromatic sulfonamide inhibitors of carbonic anhydrase. Methods of preparing probes of the invention, intermediates used in such methods, and methods of using the probes of the invention in hybridization assays are also provided. A probe of the invention is detected by binding to it a reporter group, such as a homopolymer or heteropolymer of enzymes, which includes a carbonic anhydrase which binds to the inhibitor linked to the probe, and then detecting the bound reporter group, as by production of a fluorescent or colored product in a reaction catalyzed by an enzyme component of the reporter group. Also provided are enzyme immunoassays wherein detection of antibody is by a process which comprises a chemical reaction catalyzed by a carbonic anhydrase.

Abstract: Reaction of a ketoxime-derivatized resin with a strong acid salt of aspartic anhydride or glutamic anhydride yields a novel aspartyl or glutamyl ketoxime ester-derivatized resin, wherein the aspartyl or glutamyl groups are esterified predominantly at the .alpha.-carboxyl group and wherein the aspartyl or glutamyl groups are not covalently protected at the amino group or the carboxyl group that is not esterified. Aminolysis in the presence of a weak acid of the novel aspartyl or glutamyl ketoxime ester-derivatized resin, wherein the aspartyl or glutamyl groups remain as the strong acid salt, with a salt of an amino acid with a base or an amino acid ester yields the corresponding dipeptide or dipeptide ester. After aminoylsis, the ketoxime-derivatized resin can be reused. An advantageous solid-phase method is thus provided for making .alpha.-L-aspartyl dipeptide ester sweeteners, including aspartame, and the immunopotentiating dipeptide, .alpha.-L-glutamyl-L-asparagine.

Abstract: Reaction of a ketoxime-derivatized resin with a strong acid salt of aspartic anhydride or glutamic anhydride yields a novel aspartyl or glutamyl ketoxime ester-derivatized resin, wherein the aspartyl or glutamyl groups are esterified predominantly at the .alpha.-carboxyl group and wherein the aspartyl or glutamyl groups are not covalently protected at the amino group or the carboxyl group that is not esterified. Aminolysis in the presence of a weak acid of the novel aspartyl or glutamyl ketoxime ester-derivatized resin, wherein the aspartyl or glutamyl groups remain as the strong acid salt, with a salt of an amino acid with a base or an amino acid ester yields the corresponding dipeptide or dipeptide ester. After aminolysis, the ketoxime-derivatized resin can be reused. An advantageous solid-phase method is thus provided for making .alpha.-L-aspartyl dipeptide ester sweeteners, including aspartame, and the immunopotentiating dipeptide, .alpha.-L-glutamyl-L-asparagine.