Comparison of stability, cellular, glucose-lowering and appetite supressing effects of oxyntomodulin analogues modified at the N-terminus

AM Lynch, P Patahk, YE Flatt, Victor Gault, Finbarr O'Harte, Nigel Irwin, Peter Flatt

Research output: Contribution to journalArticle

13 Citations (Scopus)


Oxyntomodulin (Oxm) possesses beneficial biological actions for the potential treatment of obesity-diabetes. However, rapid inactivation by dipeptidyl peptidase-4 (DPP-4) results in a short half-life, hindering therapeutic applicability. In the present study, six Oxm analogues namely, (Thr2)Oxm, (Asp3)Oxm, (Aib2)Oxm, (d-Ser2)Oxm, (N-acetyl)Oxm and (d-Ser2)Oxm-Lys-γ-glutamyl-PAL were synthesised and tested for DPP-4 stability and biological activity. Native Oxm, (Thr2)Oxm and (Asp3)Oxm were rapidly degraded by DPP-4, while (Aib2)Oxm, (d-Ser2)Oxm, (N-acetyl)Oxm and (d-Ser2)Oxm-Lys-γ-glutamyl-PAL were resistant to degradation. All peptides stimulated cAMP production (P
Original languageEnglish
Pages (from-to)69-78
JournalEuropean Journal of Pharmacology
Publication statusPublished - 22 Sep 2014


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