Conjugation of Peptides
AssigneeNovo Nordisk A/S
InventorsMagali A. Zundel, Bernd Peschke, Florencio Zaragoza Dorwald, Niels Peter Fiil, Nils Langeland Johansen, Henning Ralf Stennicke
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Abstract
Methods for the selective conjugation of peptides which comprises an enzymatic incorporation of a functional group at the C-terminal end of a peptide followed by reaction with a second compound comprising the moiety to be conjugated to the peptide, wherein said second compound comprises a functional group which selectively reacts with the incorporated functional group.
Claims32
A method for preparing a conjugated peptide, said method comprising the steps of
- i) reacting in one or more steps a peptide with a first compound bearing one or more functional groups, which are not accessible in any of the amino acids residues constituting said peptide, in the presence of an enzyme capable of catalysing the incorporation of said first compound into the C-terminal of said peptide to form a transacylated peptide, and
- ii) reacting in one or more steps said transacylated peptide with a second compound comprising one or more functional groups, wherein said functional group(s) do not react with functional groups accessible in the amino acid residues constituting said peptide, and wherein said functional group(s) in said second compound is capable of reacting with said functional group(s) in said first compound so that one or more covalent bond between said transacylated peptide and said second compound is formed.
A compound according for formula I
- wherein A and E independently represent C1-6alkylene, C2-6alkenylene, C2-6alkynylene or arylene, all of which may optionally be substituted with one or more substituents selected from halogen, amino, cyano and nitro;
- B and D represents —C(O)— or —NH— with the proviso that when B represents —C(O)— then D must represent —NH—, and when B represents —NH— then D must represent —C(O)—;
- and F represents hydrogen or C1-6alkylene, C2-6alkenylene, C2-6alkynylene or arylene, all of which may optionally be substituted with one or more substituents selected from halogen, amino, cyano and nitro.
A compound according to formula II
- wherein J and L independently represent C1-6alkylene, C2-6alkenylene, C2-6alkynylene or arylene, all of which may optionally be substituted with one or more substituents selected from halogen, amino, cyano and nitro;
- and M represents hydrogen or C1-6alkyl.
A compound according to formula 25 selected from the group consisting of:
- (2S)-Amino-3-[4-(2-oxopropoxy)phenyl]propionamide,
- (2S)-Amino-3-[4-(2-oxobutoxy)phenyl]propionamide,
- (2S)-Amino-3-[4-(2-oxopentoxy)phenyl]propionamide, and
- (2S)-Amino-3-[4-(4-oxopentoxy)phenyl]propionamide.
A compound according to formula III
- wherein Q represents represent C1-6alkylene, C2-6alkenylene, C2-6alkynylene or arylene, all of which may optionally be substituted with one or more substituents selected from halogen, amino, cyano and nitro;
- and T represents hydrogen or C1-6alkyl.
A compound according to formula IV
- wherein J″ and L″ independently represent C1-6alkylene or arylene, all of which may optionally be substituted with one or more substituents selected from halogen amino, cyano and nitro.
A method for conjugating a first peptide, wherein said peptide comprises an alkyne group, the method comprising reacting said first peptide with a second compound, wherein said second compound comprises a nitri-oxide to form a conjugated peptide, wherein said first peptide is bonded to said second compound via a isoxazoline moiety.
A method for conjugating a first peptide, wherein said peptide comprises an nitril-oxide group, the method comprising reacting said first peptide with a second compound, wherein said second compound comprises an alkyne to form a conjugated peptide, wherein said first peptide is bonded to said second compound via a isoxazoline moiety.
Dependencies are inferred from the claim text.