Photochemical approach to c-terminal a-amidation
OwnerMichael Richard Harris, Sydnee Wong +6inventors
InventorsMichael Richard Harris, Sydnee Wong, David Thomas Hymel, Wouter Frederik Johan Hogendorf, Felix Wojcik, Nicholas Raymond Cox, Benjamin Matthew Williams, Asmus Ringlebjerg Mortensen
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Abstract
The present invention relates to a photochemical process for the manufacturing of a C-terminal α-amide, which are a class of compounds that represent up to half of all biologically relevant peptide hormones. The invention provides mild, broad in scope, economically efficient process, which is suitable for large scale manufacturing.
Claims17
A method for producing a peptide or protein comprising a C-terminal α-amide of formula IV, following Scheme 1
- wherein R2 is a polypeptide,
- R1-X is a photolabeling agent, wherein R1 is a photolabel and X is a leaving group,
- R3 is selected from the group consisting of hydrogen, methyl and ethyl,
- comprising the steps of
- Step (a). coupling a peptide or protein comprising a C-terminal cysteine amidation tag of formula I with the photolabel (R1) to obtain a peptide-photolabel conjugate of formula II;
- Step (b). irraditating the peptide-photolabel conjugate of formula II to obtain a C-terminal enamide of formula III via a photochemical conversion;
- and
- Step (c). cleaving the resulting C-terminal enamide of formula III to obtain the C-terminal α-amide of formula IV.
A method for producing a peptide or protein comprising a C-terminal α-amide of formula IV following Scheme 2,
- wherein R2 is a polypeptide comprising an amino acid sequence as set out in SEQ ID No. 16,
- R3 is hydrogen,
- comprising the steps of
- Step (a). coupling a peptide or protein comprising a C-terminal cysteine amidation tag of formula I with 4-chloro-7-nitrobenzofurpazan to obtain a peptide-photolabel conjugate of formula II-a;
- Step (b). irradiating the peptide-photolabel conjugate of formula II-a with light having a wavelength between 400-450 nm to obtain a C-terminal enamide of formula III via photochemical conversion;
- and
- Step (c). cleaving the C-terminal enamide of formula III to obtain the C-terminal α-amide of formula IV.
(canceled)
Dependencies are inferred from the claim text.