Synthesis of an MIF-1 analogue containing enantiopure (S)-α-trifluoromethyl-proline and biological evaluation on nociception.
The synthesis and the effect of a novel MIF-1 analogue on nociception during acute pain in rat model are reported. The synthesis of this enantiopure trifluoromethyl group containing tripeptide was performed through a peptide coupling reaction between the HCl. Leu-Gly-NH2 and the (S)-α-Tfm-proline. The analgesic effect of the CF3-(MIF-1) 2 has been evaluated in vivo on rat model by paw pressure (PP) and hot plate (HP) tests and compared to the native peptide MIF-1. Highest analgesic effect was observed with CF3-(MIF-1) 2 only in PP test. In order to study the mechanisms of nociception induced by the studied peptides, the involvement of the opioid and the nitric oxideergic systems was investigated. The results are in favor of a participation of both system since pretreatment, 20 min before injection of the CF3-(MIF-1) 2, with the non-competitive antagonist of opiate receptors naloxone, the nitric oxide synthase (NOS) inhibitor l-N(G)-nitroarginine ester (l-NAME) or the nitric oxide (NO) donor l-arginine (l-Arg) significantly decreased the pain perception in PP and HP tests.
Laboratoire SOSCO, Université de Cergy-Pontoise, EA 4505, 5 Mail Gay Lussac, Neuville sur Oise, 95000 Cergy-Pontoise Cedex, France.
Ibtissem
I
Jlalia
Nathalie
N
Lensen
Grégory
G
Chaume
Elena
E
Dzhambazova
Liountmila
L
Astasidi
Radka
R
Hadjiolova
Adriana
A
Bocheva
Thierry
T
Brigaud
D059787:Acute Pain / Q000188:drug therapy*; D000818:Animals; D004195:Disease Models, Animal; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D008297:Male; D008968:Molecular Conformation; D015394:Molecular Structure; D009292:Narcotic Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D059225:Nociception / Q000187:drug effects*; D009842:Oligopeptides / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
D009292:Narcotic Antagonists; D009842:Oligopeptides; C583776:alpha-trifluoromethylprolyl-leucyl-glycinamide; D009075:MSH Release-Inhibiting Hormone