TY - JOUR
T1 - Comparison of stability, cellular, glucose-lowering and appetite supressing effects of oxyntomodulin analogues modified at the N-terminus
AU - Lynch, AM
AU - Patahk, P
AU - Flatt, YE
AU - Gault, Victor
AU - O'Harte, Finbarr
AU - Irwin, Nigel
AU - Flatt, Peter
PY - 2014/9/22
Y1 - 2014/9/22
N2 - 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
AB - 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
U2 - 10.1016/j.ejphar.2014.09.018
DO - 10.1016/j.ejphar.2014.09.018
M3 - Article
SN - 1879-0712
VL - 743
SP - 69
EP - 78
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
ER -
