Abstract: Cytotoxic variants of human ribonuclease 1 (RNase 1) identified through analysis of the interaction between RNase 1 and the human ribonuclease inhibitor (hRI) as defined by the three dimensional (3-D) atomic structure of the RNase1 hRI complex are disclosed. Also disclosed is the 3-D structure of the hRI.RNase 1 complex and methods for designing and using the RNase 1 variants.

Abstract: This invention relates to altered forms of members of the RNase A superfamily. An RNase A can be modified to be cytotoxic by altering its amino acid sequence so that it is not bound easily by the ribonuclease inhibitor while still retaining catalytic properties. While earlier work had identified some modifications to RNase A that would result in cytotoxicity, the use of the FADE algorithm for molecular interaction analysis has led to several other locations that were candidates for modification. Some of those modifications did result in RNase A variants with increase cytotoxicity.

Abstract: A class of anionic oligomers and polymers that function for inhibition of nucleases, particularly RNase. Specific inhibitors include mixtures of oligomers of vinyl sulfate. Methods for inhibition or inactivation of one or more nucleases in vitro which comprises the step of contacting the one or more nucleases in a biological medium with one or more of the anionic oligomeric or polymeric inhibitors of this invention. Kits for carrying out a biological procedure, biological reaction and/or a biological assay containing one or more inhibitors of this invention. The use of oligomers and/or polymers of this invention as additives in buffers or reagents. The inhibitors of the invention can also be attached to surfaces to provide for removal of nucleases from media, solutions or other liquids in contact with the solid.

Abstract: Cytotoxic variants of human ribonuclease 1 (RNase 1) identified through analysis of the interaction between RNase 1 and the human ribonuclease inhibitor (hRI) as defined by the three dimensional (3-D) atomic structure of the RNase1 hRI complex are disclosed. Also disclosed is the 3-D structure of the hRI·RNase 1 complex and methods for designing the RNase 1 variants.

Abstract: This invention relates to altered forms of members of the RNase A superfamily. An RNase A can be modified to be cytotoxic by altering its amino acid sequence so that it is not bound easily by the ribonuclease inhibitor while still retaining catalytic properties. While earlier work had identified some modifications to RNase A that would result in cytotoxicity, the use of the FADE algorithm for molecular interaction analysis has led to several other locations that were candidates for modification. Some of those modifications did result in RNase A variants with increase cytotoxicity.

Abstract: The present invention relates to a recognition that an analog of ?KG can increase glucose-induced insulin secretion in vitro and in vivo in animals, particularly in mammals, and more particularly in humans and in rodents. By employing the methods of the invention, insulin secretion can be increased.

Abstract: Methods and kits for covalently joining a 3? nucleic acid fragment having a 5?-hydroxyl terminus to a 5? nucleic acid fragment having a 3?-phosphate terminus are disclosed. The methods include the step of contacting the 3?-phosphate terminus of a first nucleic acid molecule and the 5?-hydroxyl terminus of a second nucleic acid molecule with an isolated 2?,3?-cyclic phosphate RNA ligase (RtcB) and a purine triphosphate in the presence of manganese (II) ion, whereby the 3?-phosphate terminus of the first nucleic acid molecule and the 5?-hydroxyl terminus of the second nucleic acid molecule are covalently joined. Although the purine triphosphate used is generally GTP or dGTP, if the method is performed in the presence of an Archease, any purine triphosphate may be used. Accordingly, the disclosed kits include isolated RtcB, along with a purine triphosphate and/or an isolated Archease.

Abstract: Methods for enhancing cellular uptake of cargo molecules by boronating the cargo molecule, particularly with one or more phenylboronic acid groups. Cellular uptake includes at least partial uptake into the cytosol. Boronation includes ligating, crosslinking or otherwise bonding one or more phenylboronic acids substituted to contain a reactive group to a cargo molecule. Boronation also includes ligating, crosslinking or otherwise bonding a phenylboronated oligopeptide to a cargo molecule. The phenylboronate groups are optionally conjugated to the cargo molecule via linking moieties that can be selectively cleaved, such cleavable linkers can allow the phenylboronate groups to be removed from the cargo molecule after the boronated cargo molecule is introduced into the cell. The invention includes certain phenylboronates which are boronation reagents, certain boronated oligopeptides and certain boronated peptides and proteins.

Abstract: A class of anionic oligomers and polymers that function for inhibition of nucleases, particularly RNase. Specific inhibitors include mixtures of oligomers of vinyl sulfate. Methods for inhibition or inactivation of one or more nucleases in vitro which comprises the step of contacting the one or more nucleases in a biological medium with one or more of the anionic oligomeric or polymeric inhibitors of this invention. Kits for carrying out a biological procedure, biological reaction and/or a biological assay containing one or more inhibitors of this invention. The use of oligomers and/or polymers of this invention as additives in buffers or reagents. The inhibitors of the invention can also be attached to surfaces to provide for removal of nucleases from media, solutions or other liquids in contact with the solid.

Abstract: Water soluble reagents and methods for the formation of an amide bond between a phosphinothioester and an azide in an aqueous medium. The phosphinothioester is generated using a water-soluble phosphinothiol reagent. This reaction allows formation of an amide bond between a wide variety of chemical species including amino acids, peptides or protein fragments in an aqueous solution. Of particular interest, this reaction allows for the formation of an amide bond in a physiological setting. In a specific embodiment, this invention provides reagents and methods for peptide ligation in an aqueous medium. The reaction eliminates the need for a cysteine residue and is traceless leaving no residual atoms in the ligated peptide product.

Abstract: Cytotoxic variants of human ribonuclease 1 (RNase 1) identified through analysis of the interaction between RNase 1 and the human ribonuclease inhibitor (hRI) as defined by the three dimensional (3-D) atomic structure of the RNase1 hRI complex are disclosed. Also disclosed is the 3-D structure of the hRI·RNase 1 complex and methods for designing the RNase 1 variants.

Abstract: This invention relates to altered forms of members of the RNase A superfamily. An RNase A can be modified to be cytotoxic by altering its amino acid sequence so that it is not bound easily by the ribonuclease inhibitor while still retaining catalytic properties. While earlier work had identified some modifications to RNase A that would result in cytotoxicity, the use of the FADE algorithm for molecular interaction analysis has led to several other locations that were candidates for modification. Some of those modifications did result in RNase A variants with increase cytotoxicity.

Abstract: This invention relates to cytotoxic variants of human ribonuclease 1 (RNase 1) identified through analysis of the interaction between RNase 1 and the human ribonuclease inhibitor (hRI) as defined by the three dimensional (3-D) atomic structure of the RNase1 hRI complex. Also disclosed is the 3-D structure of the hRI•RNase 1 complex and methods for designing the RNase 1 variants.

Abstract: This invention relates to altered forms of members of the RNase A superfamily. An RNase A can be modified to be cytotoxic by altering its amino acid sequence so that it is not bound easily by the ribonuclease inhibitor while still retaining catalytic properties. While earlier work had identified some modifications to RNase A that would result in cytotoxicity, the use of the FADE algorithm for molecular interaction analysis has led to several other locations that were candidates for modification. Some of those modifications did result in RNase A variants with increase cytotoxicity.

Abstract: Methods and reagents for site-selective functionalization of peptides and proteins. The methods most generally involve the reaction of a thioester with hydrazine. Reagents include bifunctional reagents of formula: H2N—NH—CH2-M-L-FG and salts thereof where M is a single bond or a chemical group carrying a non-bonding electron pair, such as —C(O)NR?—, where R? is H, or an alkyl or aryl group; L is an optional linker group as described above; and FG is a functional group having reactivity that is orthongonal to that of the hydrazine group. FG can, among others, be an azide, alkenyl, alkynyl, nitrile (—CN) or triazole group and is preferably an azide group (—N3). Methods and reagents can, for example, be combined with intein-mediated protein splicing to link proteins or fragments thereof to various chemical species or to a surface.

Abstract: This invention relates to cytotoxic variants of human ribonuclease 1 (RNase 1) identified through analysis of the interaction between RNase 1 and the human ribonuclease inhibitor (hRI) as defined by the three dimensional (3-D) atomic structure of the RNase1 hRI complex. Also disclosed is the 3-D structure of the hRI•RNase 1 complex and methods for designing the RNase 1 variants.

Abstract: This invention relates to altered forms of members of the RNase A superfamily. An RNase A can be modified to be cytotoxic by altering its amino acid sequence so that it is not bound easily by the ribonuclease inhibitor while still retaining catalytic properties. While earlier work had identified some modifications to RNase A that would result in cytotoxicity, the use of the FADE algorithm for molecular interaction analysis has led to several other locations that were candidates for modification. Some of those modifications did result in RNase A variants with increase cytotoxicity.

Abstract: This invention relates to cytotoxic variants of human ribonuclease 1 (RNase 1) identified through analysis of the interaction between RNase 1 and the human ribonuclease inhibitor (hRI) as defined by the three dimensional (3-D) atomic structure of the RNase1 hRI complex. Also disclosed is the 3-D structure of the hRI•RNase 1 complex and methods for designing the RNase 1 variants.

Abstract: Latent fluorescent compounds, comprising a fluorescent molecule with one or more blocking groups attached and optionally one or more urea-containing groups are provided. The urea-containing group can be used to further attach one or more molecules of interest, such as proteins, peptides or nucleic acids. The blocking group(s) is released from the latent fluorescent compound by reaction with a trigger, forming the fluorescent molecule which can be detected. Also provided herein are methods of using latent fluorescent compounds to detect triggers.

Abstract: Methods and compositions involving a class of boron-protected phenylphosphine agents having increased cell permeability and having improved chemical stability for treating or for preventing neuronal cell death-related diseases or conditions in a human or a non-human animal.