Solid phase native chemical ligation of unprotected or N-terminal cysteine protected peptides in aqueous solution
AssigneeGryphon Therapeutics, Inc.
InventorsLynne Canne, Stephen B. H. Kent, Reyna Simon
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Abstract
The present invention provides methods, apparatus and kits for synthesizing assembled peptides and proteins on a solid phase with sequential ligation of three or more unprotected peptide segments using chemoselective and mild ligation chemistries in aqueous solution. Also provided are methods of monitoring solid phase sequential ligation reactions using MALDI or electrospray ionization mass spectrometry of reaction products.
Claims20
An apparatus for producing assembled polypeptides, said apparatus comprising a reaction vessel containing as components:
- (a) a solid phase support having bound thereto a plurality of first peptides, said first peptides comprising partially or completely unprotected peptides having an N-terminus that is bound to said solid phase support via a cleavable handle, and a C-terminus that comprises a thioacid or a thioester;
- (b) a plurality of second peptides comprising partially or completely unprotected peptides having an N-terminal cysteine and a C-terminal thioester or thioacid.
An apparatus for preparing assembled polypeptides, said apparatus comprising a reaction vessel containing as components:
- a) a solid phase support having bound thereto a plurality of first peptides, said first peptides comprising partially or completely unprotected peptides having a C-terminus that is bound to said solid phase support via a cleavable linkage and an N-terminus that comprises a cysteine residue;
- b) a plurality of second peptides comprising partially or completely unprotected peptides having an N-terminal cysteine and a C-terminal thioacid or thioester.
Dependencies are inferred from the claim text.