Nociceptin/orphanin FQ (N/OFQ) controls different biological functions via selective stimulation of the N/OFQ peptide (NOP) receptor. The pleiotropic actions of N/OFQ may limit the development of NOP ligands as innovative drugs in different therapeutic areas. The pharmacological concept of functional selectivity (aka biased agonism) might be useful for amplifying beneficial actions and/or counteracting side effects. Thus, molecules with large bias factors toward G protein or β arrestin are required for investigating the translational value of NOP biased modulation. Herein, the biased behavior of a heterogeneous library of NOP-targeting peptide derivatives was evaluated in vitro with the aim to provide possible insights into the structural determinants that govern the selective activation of G protein versus β-arrestin. Our results demonstrate that lipidation of N/OFQ(1–13)-NH₂ is a useful strategy for obtaining G protein biased agonists for the NOP receptor.

中文翻译：

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Nociceptin / orphanin FQ受体的偏向激动作用：对N / OFQ（1-13）-NH2的结构活性研究。

Nociceptin / orphanin FQ（N / OFQ）通过选择性刺激N / OFQ肽（NOP）受体来控制不同的生物学功能。N / OFQ的多效性作用可能会限制NOP配体在不同治疗领域中作为创新药物的发展。功能选择性（又称偏向激动作用）的药理学概念可能对放大有益作用和/或抵消副作用有用。因此，需要对G蛋白或β抑制蛋白具有较大偏倚因子的分子来研究NOP偏向调节的翻译值。在此，在体外评估了靶向NOP的肽衍生物异构库的偏向行为目的是对控制G蛋白与β-arrestin选择性激活的结构决定因素提供可能的见解。我们的结果表明，N / OFQ（1-13）-NH _2的脂化作用是获得针对NOP受体的G蛋白偏向激动剂的有用策略。