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Recombinant Fusion of Glucagon-Like Peptide-1 and an Albumin Binding Domain Provides Glycemic Control for a Week in Diabetic Mice

Publication ,  Journal Article
Yousefpour, P; Varanko, A; Subrahmanyan, R; Chilkoti, A
Published in: Advanced Therapeutics
October 1, 2020

Glucagon-like peptide-1 (GLP1) is an intestinally derived incretin currently under investigation for treatment of type 2 diabetes. The clinical application of GLP1 is limited by its short half-life, which necessitates frequent administration. To address this challenge, GLP1 is recombinantly synthesized as a fusion to an albumin binding domain (ABD). The native GLP1 sequence is engineered to inhibit an inactivating cleavage site and a rigid helical linker (HL) is utilized between the GLP1 and ABD to reduce interference of albumin binding by the ABD upon the ability of GLP1 to bind and activate its receptor. Upon subcutaneous administration (SC), the GLP1-HL-ABD fusion binds to endogenous albumin and exhibits an extended half-life of ≈44 h in mice. In a diabetic (db/db) mouse model, a single SC injection of GLP1-HL-ABD affords up to 7 d of glycemic control, which is significantly longer than the ≈12 h duration of glucose control provided by liraglutide, an albumin binding fatty acid derivative of GLP1 currently on the market for treatment of type 2 diabetes.

Duke Scholars

Published In

Advanced Therapeutics

DOI

EISSN

2366-3987

Publication Date

October 1, 2020

Volume

3

Issue

10

Related Subject Headings

  • 3214 Pharmacology and pharmaceutical sciences
  • 3206 Medical biotechnology
  • 3101 Biochemistry and cell biology
 

Citation

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ICMJE
MLA
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Yousefpour, P., Varanko, A., Subrahmanyan, R., & Chilkoti, A. (2020). Recombinant Fusion of Glucagon-Like Peptide-1 and an Albumin Binding Domain Provides Glycemic Control for a Week in Diabetic Mice. Advanced Therapeutics, 3(10). https://doi.org/10.1002/adtp.202000073
Yousefpour, P., A. Varanko, R. Subrahmanyan, and A. Chilkoti. “Recombinant Fusion of Glucagon-Like Peptide-1 and an Albumin Binding Domain Provides Glycemic Control for a Week in Diabetic Mice.” Advanced Therapeutics 3, no. 10 (October 1, 2020). https://doi.org/10.1002/adtp.202000073.
Yousefpour P, Varanko A, Subrahmanyan R, Chilkoti A. Recombinant Fusion of Glucagon-Like Peptide-1 and an Albumin Binding Domain Provides Glycemic Control for a Week in Diabetic Mice. Advanced Therapeutics. 2020 Oct 1;3(10).
Yousefpour, P., et al. “Recombinant Fusion of Glucagon-Like Peptide-1 and an Albumin Binding Domain Provides Glycemic Control for a Week in Diabetic Mice.” Advanced Therapeutics, vol. 3, no. 10, Oct. 2020. Scopus, doi:10.1002/adtp.202000073.
Yousefpour P, Varanko A, Subrahmanyan R, Chilkoti A. Recombinant Fusion of Glucagon-Like Peptide-1 and an Albumin Binding Domain Provides Glycemic Control for a Week in Diabetic Mice. Advanced Therapeutics. 2020 Oct 1;3(10).

Published In

Advanced Therapeutics

DOI

EISSN

2366-3987

Publication Date

October 1, 2020

Volume

3

Issue

10

Related Subject Headings

  • 3214 Pharmacology and pharmaceutical sciences
  • 3206 Medical biotechnology
  • 3101 Biochemistry and cell biology