Neuromedin U (NMU) mediates various physiological functions via NMUR1 and NMUR2 receptors. NMUR2 has been considered a promising treatment option for diabetes and obesity. Although NMU-8, a shorter peptide, has potent agonist activity for both receptors, it is metabolically unstable. Therefore, NMU-8 analogs modified with long-chain alkyl moieties via a linker were synthesized. An octadecanoyl analog (17) with amino acid substitutions [αMePhe¹⁹, Nle²¹, and Arg(Me)²⁴] and a linker [Tra-γGlu-PEG(2)] dramatically increased NMUR2 selectivity, with retention of high agonist activity. Subcutaneous administration of 17 induced anorectic activity in C57BL/6J mice. Owing to its high metabolic stability, 17 would be useful in clarifying the physiological role and therapeutic application of NMU.

Neuromedin U（NMU）通过NMUR1和NMUR2受体介导各种生理功能。NMUR2被认为是糖尿病和肥胖症的有前途的治疗选择。尽管NMU-8（一种较短的肽）对两种受体都具有有效的激动剂活性，但它在代谢上是不稳定的。因此，合成了通过接头用长链烷基部分修饰的NMU-8类似物。十八烷类似物（17）具有氨基酸取代[αMePhe ¹⁹，NLE ²¹，和Arg（Me）中²⁴ ]和接头[TRA-的γGlu-PEG（2）]急剧增加NMUR2选择性，具有高激动剂活性的保留。皮下注射17诱导C57BL / 6J小鼠的厌食活动。由于其高代谢稳定性，图17将有助于阐明NMU的生理作用和治疗应用。