Abstract: Exendin-4 (EX-4) is a drug candidate with established potential for treatment of type II diabetes. It has been found that one of its analogs with the substitutions of both β-Asp for Glu3 and Tyr for Gln13 have a prolongation in biological half life, an increase in cell proliferation and a remarkable improvement in reducing blood sugar with respect to EX-4. In this paper, we studied the structures of both EX-4 and this EX-4 analog in SDS micelles by NMR spectroscopy. The results showed that both EX-4 and its analog adopt α-helix structures with the N-termini disordered and the C-terminal parts folded as Trp-cage in the medium, but the EX-4 analog contains more helical turns in the N-terminal region than EX-4. The extension of helix to the N-terminus may favor affinity for extracellular domain of GLP-1 receptor and accurate positioning of the crucial N-terminal residues in the transmembrane domains responsible for receptor activation.

Key words: Exendin-4 analog, Structure, NMR