Process of Preparing Guanylate Cyclase C Agonists
AssigneeSynergy Pharmaceuticals, Inc.
InventorsJuncai Bai, Ruoping Zhang, Jun Jian, Junfeng Zhou, Qiao Zhao, Guoquing Zhang, Kunwar Shailubhai, Stephen Comiskey, Rong Feng
Life of this patent
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Abstract
The invention provides processes of preparing a peptide including a GCC agonist sequence selected from the group consisting of SEQ ID NOs: 1-249 described herein.
Claims29
A process of preparing a peptide comprising a GCC agonist sequence selected from the group consisting of SEQ ID NOs:
- 1-249, wherein the GCC agonist sequence is n amino acid units in length, with the N-terminal unit at position 1 and the C-terminal unit at position n, the process comprising:
- providing a first fragment having a first sequence of amino acid units from position j through position k of the GCC agonist sequence, wherein j is an integer between 1 and n−1, k is an integer between 2 and n and is greater than j, and the first fragment is protected except for an amino group of the amino acid unit at position j, or alternatively, a carboxyl group of the amino acid unit at position k,
- providing a second fragment having a second sequence of amino acid units from position h through position j−1 of the GCC agonist sequence or having a third sequence of amino acid units from position k+1 through position m of the GCC agonist sequence, wherein h is an integer between 1 and n−2 and is smaller than j, m is an integer between k+2 and n, and the second fragment is protected except for a carboxyl group of the amino acid unit at position j−1 or an amino group of the amino acid unit at position k+1, and
- coupling the first and the second fragments via a solution-phase synthesis to yield a protected peptide having a sequence of amino acid units from position h through position k of the GCC agonist sequence or a protected peptide having a sequence of amino acid units from position j through position m of the GCC agonist sequence.
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A process of purifying the peptide comprising the GCC agonist sequence selected from the group consisting of SEQ ID NOs:
- 1-249, the process comprising adsorbing the peptide onto a polymeric adsorbent column, desalting the peptide, eluting the desalted peptide off the polymeric adsorbent column with an alcohol aqueous solution to form a peptide solution, removing water from the peptide solution, and adding an ether to the dewatered peptide to precipitate the peptide.
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A purified peptide comprising the GCC agonist sequence selected from the group consisting of SEQ ID NOs:
- 1-249, wherein the peptide has a bulk density of no less than 0.1 g/mL, no less than 0.2 g/mL, no less than 0.3 g/mL, no less than 0.4 g/mL, or no less than 0.5 g/mL.
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Dependencies are inferred from the claim text.