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US 2009/0264366 A1Published application
Transglutaminase Mediated Conjugation of Peptides
AssigneeNovo Nordisk Healthcare AG
InventorsNils Langeland Johansen, Magali Zundel, Florencio Zaragoza Dorwald
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Abstract
Methods for conjugating peptides are provided comprising i) reacting a peptide with a first compound comprising a functional group in the presence of a transglutaminase capable of incorporating said compound into the peptide to form a transaminated peptide, and ii) reacting said transaminated peptide with e.g. a functionalized polymer capable of reacting with the functional group incorporated in the peptide in the enzymatic reaction.
Claims38
A method for producing a conjugated peptide comprising:
- a) reacting, in one or more steps, a peptide with a first compound comprising one or more functional groups or latent functional groups, which are not accessible in any of the amino acids residues constituting said peptide, in the presence of transglutaminase capable of catalyzing the incorporation of said first compound into said peptide to form a functionalized peptide;
- b) optionally activating a present latent functional group;
- and
- c) reacting, in one or more steps, said functionalized peptide with a second compound comprising one or more functional groups, wherein said functional group(s) (I) do not react with functional groups accessible in the amino acid residues constituting said peptide and (II) are capable of reacting with said functional group(s) in said first compound so that a covalent bond between said functionalized peptide and said second compound is formed thereby producing a conjugated peptide.
1 more element
A composition consisting of:
- (a) a compound according to the formula:
- wherein
- P—C(O)—NH— represents the peptide radical obtained by removing a hydrogen from —NH2 in the side chain of Gln;
- D represents a bond or oxygen;
- R represents a linker or a bond;
- E represents a linker or a bond;
- A represents an oxime, hydrazone, phenylhydrazone, semicarbazone, triazole or isooxazolidine moiety;
- and
- Z is selected amongst PEG or mPEG radicals and amino derivatives thereof (including straight and branched PEG and mPEG radicals);
- straight, branched and/or cyclic C1-22alkyl, C2-22alkenyl, C2-22alkynyl, C1-22heteroalkyl, C2-22heteroalkenyl, C2-22heteroalkynyl, wherein one or more homocyclic aromatic compound biradical or heterocyclic compound biradical may be inserted, and wherein said C1-C22 or C2-C22 radicals may optionally be substituted with one or more substituents selected from hydroxyl, halogen, carboxyl, heteroaryl and aryl, wherein said aryl or heteroaryl may optionally be further substituted by one or more substituents selected from hydroxyl, halogen, and carboxyl;
- steroid radicals;
- lipid radicals;
- polysaccharide radicals;
- dextrans;
- polyamide radicals;
- polyamino acid radicals;
- PVP radicals;
- PVA radicals;
- poly(1-3-dioxalane);
- poly(1,3,6-trioxane);
- ethylene/maleic anhydride polymer;
- Cibacron dye stuffs;
- or Cibacron Blue 3GA;
- (b) a pharmaceutically acceptable salt of a compound according to (a);
- (c) a prodrug of a compound according to (a);
- or
- (d) a solvate of a compound according to (a).
24 more elements
Dependencies are inferred from the claim text.