45 results about "Norleucine" patented technology

Some embodiments relate to analogs of peptides corresponding to class I MHC-restricted T cell epitopes and methods for their generation. These analogs can contain amino acid substitutions at residues that directly interact with MHC molecules, and can confer improved, modified or useful immunologic properties. Additionally classes of analogs, in which the various substitutions comprise the non-standard residues norleucine and/or norvaline, are disclosed.

The instant invention is drawn to the methods and compositions necessary to provide recombinant proteins with a substantially reduced or eliminated content of norleucine or other non-standard amino acids. Various embodiments of the invention provide for the substantial elimination of the incorporation of non-standard amino acids into recombinant proteins by the co-expression or enhanced expression of a protein (or the enzymatically active portion thereof) capable of degrading norleucine or other non-standard amino acids, including norvaline, beta-methylnorleucine, and homoisoleucine. In certain particular embodiments of the invention, the norleucine is degraded by a glutamate dehydrogenase, a leucine dehydrogenase, a valine dehydrogenase, a phenylalanine dehydrogenase, a glutamate/leucine/phenylalanine/valine dehydrogenase, or an opine dehydrogenase. Also provided are the cells and DNA constructs for carrying out these methods.

The present invention relates to methods and compositions for preventing incorporation of norleucine into proteins during recombinant protein production in bacteria. The present invention also provides microorganism host cells and nucleic acid molecules for use with the methods and compositions provided herein.

A composition of variant biocatalysts, specifically variants of D-amino acid oxidases, with improved biocatalytic activity towards D-amino acid substrates such as, but not limited to, D-tert-leucine, D-norvaline, D-2-aminobutyrate, D-alanine, D-isoleucine, D-valine, D-methionine, D-hydroxyadamantlyglycine, D-penicillamine, or D-norleucine is disclosed. Further disclosed is a method of preparing enantioselective amino acids using variant D-amino acid oxidases of the present invention.

Prodrugs of glutamine analogs, such as prodrugs of aza-serine, and 6-diazo-5-oxo-norleucine (DON), and 5-diazo-4-oxo-L-norvaline (L-DONV) are disclosed.

A gastrin analog shows high uptake in CCK-2 receptor positive tumors and simultaneously a very low accumulation in the kidneys. This is achieved by a mini-gastrin analog PP-F11 having the formula: PP-F11-X-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Y-Asp-Phe-NH₂, wherein Y is an amino acid replacing methionine and X is a chemical group attached to the peptide for diagnostic and/or therapeutic intervention at CCK-2 receptor relevant diseases. Very suitable compounds with respect to a high tumor to kidney ratio are mini-gastrin analogs with six D-glutamic acids or six glutamines. These compounds still possess a methionine which can be oxidized easily which is a disadvantage for clinical application under GMP due to the forms which may occur. The elimination of the methionine leads to a lower affinity to oxidation which in general favors the tumor-kidney-ratio. Ideally, the methionine is replaced by norleucine. This PP-F11N mini gastrin exhibits currently the best tumor-kidney-ratio and is the most promising candidate.

The invention discloses an NQO1 activated type 6-diazo-5-oxo-L-n-leucine prodrug as well as a preparation method and application of thereof. NQO1 is highly expressed in most tumor cells, so a tumor targeting effect can be realized by introducing a quinonyl acid group activated by the NQO1, DON prodrugs can be efficiently and rapidly released in the tumor cells, and the purpose of inhibiting tumor proliferation is achieved. The prodrug shows high affinity to NQO1, and can rapidly, efficiently and directionally release a glutamine metabolism antagonist DON in tumor cells highly expressed by NQO1, so that the toxic and side effects of the drug are reduced, the targeting efficiency of tumor treatment is improved, and a new thought is provided for development of antitumor drugs.

Modified glucagon molecules and buffer and/or excipient solutions are provided that result in the glucagon molecules being resistant to oxidation when stored at a substantially neutral pH. Such a modified glucagon molecule includes a substitution at position 27, with the native methionine being replaced with a methionine memetic analog, a norleucine, or an isomer of either of the foregoing. Optionally, the modified glucagon molecules may be further phosphorylated to result in enhanced solubility at a substantially neutral pH and resistance to fibrillation. Methods of using such molecules in pharmaceutical compositions and therapeutic kits are also provided.

The invention concerns a peptide based on biologically active CCK-8. The peptide has improved characteristics for the treatment of at least one of obesity and type 2 diabetes and has the structure:

(Z)-Asp¹-Aaa²(X)-Aaa³Gly⁴Trp⁵Aaa⁶Asp⁷(Y)Aaa⁸K,

wherein the amino acids may be either D or L amino acids; the bond between amino acid residues is either a peptide bond or a non-peptide isostere bond; Aaa² is selected from the group comprising Tyr and Phe; when Aaa² is Tyr, X is selected from the group comprising SO₃H⁻, PO₃H₂⁻ and a polymer moiety of the general formula —O—(CH₂—O—CH₂)_n—H, in which n is an integer between 1 and about 22, wherein the X is covalently bound to the para phenyl oxygen of Tyr, and, when Aaa² is Phe, X is CH₂SO₃Na, wherein the X is covalently bound to the para phenyl position of Phe; Aaa³ is selected from the group comprising Met, norleucine, 2-aminohexanoic acid and Thr; Aaa⁶ is selected from the group comprising Met, norleucine, 2-aminohexanoic acid and Phe; Aaa⁸ is selected from the group comprising Phe and Met; Y is covalently bound to the nitrogen of Aaa⁸ and is selected from the group consisting of H and CH₃; K is selected from the group consisting of the hydroxyl group of Phe⁸, an amide covalently bound to Phe⁸, an ester covalently bound to Phe⁸, a salt of the hydroxyl group of Phe⁸, a salt of an amide covalently bound to Phe⁸, a salt of an ester covalently bound to Phe⁸ and a polymer moiety of the general formula —O—(CH₂—O—CH₂)_n—H, in which n is an integer between 1 and about 22; and Z comprises at least one amino acid modification, wherein said at least one modification comprises an N-terminal extension, or an N-terminal modification, but excludes Asp¹-glucitol CCK-8 where Aaa² is Tyr and X is SO₃H⁻.

The peptides, and Asp¹-glucitol CCK-8, are useful to at least one of inhibit food intake, induce satiety, stimulate insulin secretion, moderate blood glucose excursions, enhance glucose disposal and exhibit enhanced stability in plasma compared to native CCK-8