Insulin conjugates and methods of use thereof
The invention relates generally to chimeric peptides and compositions that facilitate the transport of insulin across biological membranes, methods for preparing the chimeric peptides, and a method for treating a subject suffering from diabetes.
1. A chimeric peptide comprising a first domain and a second domain, wherein the first domain comprises the translocation sequence of SEQ ID NO:30 which facilitates active transport across a biological membrane and the second domain comprises at least a biologically active portion of an insulin polypeptide.
2. The peptide of claim 1 , wherein the translocation sequence binds an aminoglycan.
3. The peptide of claim 2 , wherein the aminoglycan is heparin or chondroitin sulfate.
4. The peptide of claim 1 , wherein the chimeric protein translocates a physiological barrier.
5. The peptide of claim 4 , wherein physiological barrier is the gastrointestinal barrier or the blood-brain barrier.
6. The peptide of claim 1 , further comprising a third domain selected from the group consisting of:
(a) a CDR3 region of a human anti-DNA antibody;
(b) a CDR2 region of a human anti-DNA antibody;
(c) a CDR3 region of a murine anti-DNA antibody; and
(d) a CDR2 region of a murine anti-DNA antibody.
7. A composition comprising a peptide according to claim 1 or 6 and a pharmaceutically acceptable diluent, carrier or adjuvant.
8. The composition according to claim 7 in a formulation suitable for oral administration.
9. A kit comprising in one or more containers, the composition of claim 7 .
10. The chimeric peptide of claim 1 , wherein the second domain comprising at least a biologically active portion of an insulin polypeptide still has at least one function of native insulin.
11. The chimeric peptide of claim 10 , wherein the at least one function of native insulin is decreasing blood glucose levels.