Protease-resistant glucagon like peptide-1 analogs with long-term anti-diabetes type 2 activity

  • Hongjian Li
  • Cindy X Zhou
  • Zhengding Su
Part of the Advances in Experimental Medicine and Biology book series (volume 611)


Type 2 diabetes (also known as non-insulin-dependent diabetes, NIDDM) is increasing in prevalence worldwide. It is well accepted that NIDDM therapeutic approaches should rely on peptides because of the large interaction interface between glucagon like peptide-1 (GLP-1) and its cognate receptor. The size of the interface limits the efficacy of small molecule antagonists [1]. Human GLP-1 is an endogenous 30 or 31 amino acid residue peptide that occurs in two forms; GLP-1(7– 36) amide and GLP-1(7–37). Both peptides have limited therapeutic utility owing to rapid degradation in the circulation by DPP IV peptidase and susceptibility to degradation by neutral endopeptidases (e.g. NEP24.11) [2,3]. As such, the drug discovery challenge is to make a stable GLP-1-like compound with a long half-life. In last decades, GLP-1 analogs have been extensively designed using mutagenesis-based side-chain replacement, but significant progress has not occurred until Extindin-4 was developed [4]...


Peptide Bond Peptide Analog Ethyl Bond Oral Glucose Challenge Protease Resistance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was partially supported by Guangdong Key Laboratory of Biopharmacy (2006B60119) and Guangzhou Scientific and Technological Fund (2006Z3-E4152) to H. J. L and Z.D.S.


  1. 1.
    Gallwitz, B. (2006) Minerva Endocrinol. 31, 133–147.Google Scholar
  2. 2.
    Arulmozhi, D. K. & Portha, B. (2006) Eur J Pharm Sci. 28, 96–108.CrossRefGoogle Scholar
  3. 3.
    Trebbien, R.; Klarskov, L.; Olesen, M.; Holst, J. J.; Carr, R. D. & Deacon, C. F. (2004) Am. J. Physiol. Endocrinol. Metab., 287, 431–438.CrossRefGoogle Scholar
  4. 4.
    Eng, J.; Kleinman, W. A.; Singh, L.; Singh, G. & Raufman, J. P. (1992) J. Biol. Chem. 267, 7402–7408.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Hongjian Li
    • 1
  • Cindy X Zhou
    • 2
  • Zhengding Su
    • 2
    • 3
  1. 1.Depart. of BiotechnologyJinan UniversityGuangzhouChina
  2. 2.Amersino BiodevelopKitchener
  3. 3.Department of ChemistryUniversity of WaterloowaterlooCanada

Personalised recommendations