Syntheses of two neuromedin U (NMU) analogues and their comparative reducing food intake effect in rats

Summary.  To examine the roles of aromatic rings Tyr residues at positions 1 and 6 and Phe residues at positions 16, 17 and 19 of rat neuromedin U-23 (NMU-23) (Tyr-Lys-Val-Asn-Glu-Tyr-Gln-Gly-Pro-Val-Ala-Pro-Ser-Gly-Phe-Phe-Leu-Phe-Arg-Pro-Arg-Asn-NH₂) for reducing food intake activity in male Wistar rats, two NMU-23 analogues, Phe(4F)^16,17,19]NMU-23 and Tyr(Me)^1,6]NMU-23, were synthesized by Fmoc strategy of manual solid-phase method. The synthetic NMU-23 showed reducing effect on food intake in rats. Phe(4F)^16,17,19]NMU-23 exhibited higher reducing food intake effect than that of NMU-23. On the contrary, Tyr(Me)^1,6]NMU-23 showed no reducing effect on food intake in rats than that of NMU-23. Received July 6, 2002 Accepted October 30, 2002 Published online January 20, 2003 Acknowledgements We are grateful to Dr. Hiroshi Sekino of Kojinkai Central Hospital for giving us opportunities to do some experiments at Kidney Research Laboratory in Kojinkai Central Hospital in Sendai. Authors' address: Takashi Abiko, Ph. D., Research Laboratory, Global Shinwa Pharmaceutical Company, 4-17-29, Komatsushima, Aoba-ku, Sendai, 981-0905 Japan, E-mail: abiko@ma.mni.ne.jp Abbreviations: NMU, neuromedin U; TLC, thin layer chromatography; 4F, 4-fluoro; TFA, trifluoroacetic acid; Fmoc, 9-fluorenylmethoxycarbonyl; NPY, neuropeptide Y; Obu^t, tert-butoxy; Trt, trityl; HPLC, high performance liquid chromatography; FAB-MS, fast atom bombardment mass spectrometry; AcOH, acetic acid; DCC, N,N′-dicyclohexylcarbodiimide; HOBT, 1-hydroxybenzotriazole; Mts, mesitylenesulfonyl; Boc, tert-butoxycarbonyl; DMF, dimethyformamide; TMSOTf, trimethylsilyltrifrate; EtOH, ethanol.