An imidazole based H-Phe-Phe-NH2 peptidomimetic with anti-allodynic effect in spared nerve injury mice
Anna Skogh, Anna Lesniak, Christian Skold, Maria Karlgren, Fabienne Z Gaugaz, Richard Svensson, Shanti Diwakarla, Anna Jonsson, Rebecca Fransson, Fred Nyberg, Mathias Hallberg, Anja Sandstrom
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2018
The dipeptide amide H-Phe-Phe-NH2 (1) that previously was identified as a ligand for the substance P 1-7 (SP1-7) binding site exerts intriguing results in animal models of neuropathic pain after central but not after peripheral administration. The dipeptide 1 is derived from stepwise modifications of the anti-nociceptive heptapeptide SP1-7 and the tetrapeptide endomorphin-2 that is also binding to the SP1-7 site. We herein report a strong anti-allodynic effect of a new H-Phe-Phe-NH2 peptidomimetic (4) comprising an imidazole ring as a bioisosteric element, in the spare nerve injury (SNI) mice model after peripheral administration. Peptidomimetic 4 was stable in plasma, displayed a fair membr..View full abstract
Awarded by Swedish Medical Research Council
We gratefully acknowledge Kjell and Marta Beijer Foundation, the Berzelii Technology Centre for Neurodiagnostics, the Swedish Medical Research Council (Grant no. 9459) for financial support.