Proinsulin polypeptide-oligomer conjugates
First Claim
1. A proinsulin-oligomer monoconjugate comprising a proinsulin and an oligomer,wherein the proinsulin comprises an A-chain and a B-chain;
- a connecting C-peptide coupled at a first end to the C-terminus of the B-chain and coupled at a second end to the N-terminus of the A-chain polypeptide by peptide bonds; and
a leader peptide coupled to the N-terminus of the B-chain polypeptide, by a peptide bond, andwherein the oligomer comprises a hydrophilic moiety and a lipophilic moiety,wherein the hydrophilic moiety comprises at least one polyalkylene glycol moiety, andwherein the oligomer is coupled to a lysine residue of the B-Chain of the proinsulin.
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Abstract
Methods for synthesizing proinsulin polypeptides are described that include a contacting a proinsulin polypeptide including an insulin polypeptide coupled to one or more peptides by peptide bond(s) capable of being cleaved to yield the insulin polypeptide with an oligomer under conditions sufficient to couple the oligomer to the insulin polypeptide portion of the proinsulin polypeptide and provide a proinsulin polypeptide-oligomer conjugate, and cleaving the one or more peptides from the proinsulin polypeptide-oligomer conjugate to provide the insulin polypeptide-oligomer conjugate. Methods of synthesizing proinsulin polypeptide-oligomer conjugates are also described as are proinsulin polypeptide-oligomer conjugates. Methods of synthesizing C-peptide polypeptide-oligomer conjugates are also described.
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Citations
8 Claims
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1. A proinsulin-oligomer monoconjugate comprising a proinsulin and an oligomer,
wherein the proinsulin comprises an A-chain and a B-chain; - a connecting C-peptide coupled at a first end to the C-terminus of the B-chain and coupled at a second end to the N-terminus of the A-chain polypeptide by peptide bonds; and
a leader peptide coupled to the N-terminus of the B-chain polypeptide, by a peptide bond, andwherein the oligomer comprises a hydrophilic moiety and a lipophilic moiety, wherein the hydrophilic moiety comprises at least one polyalkylene glycol moiety, and wherein the oligomer is coupled to a lysine residue of the B-Chain of the proinsulin. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8)
- a connecting C-peptide coupled at a first end to the C-terminus of the B-chain and coupled at a second end to the N-terminus of the A-chain polypeptide by peptide bonds; and
Specification