Erskine-Grout M E, Olivier G W, Lucas P, Sahm U G, Branch S K, Moss S H, Notarianni L J, Pouton C W
School of Pharmacy and Pharmacology, University of Bath, UK.
Melanoma Res. 1996 Apr;6(2):89-94. doi: 10.1097/00008390-199604000-00002.
The fate of alpha-melanocyte-stimulating hormone (alpha-MSH) subsequent to binding to the melanoma melanocortin MC1 receptor is of interest with regard to its potential use in targeting cytotoxic drugs or imaging to melanoma. Tools such as iodinated, photoaffinity-labelled, biotinylated and fluorescent melanocortins are required to study the fate of the ligand during its interaction with the receptor. In this study, a series of probes for the receptor based on the potent analogue, [Nle4,Dphe7]alpha-MSH, have been developed and tested for their potential usefulness. All probes contain the core melanocortin motif His-Phe-Arg-Trp. They bind the receptor readily and appear to have similar intrinsic efficacies to the endogenous peptide, so that biological activity is regulated by their receptor binding affinity. Functional photoaffinity-labelled, biotinylated and fluorescent probes are described. The biotinylated probe binds the receptor when coupled to streptavidin, although with reduced affinity.
α-黑素细胞刺激素（α-MSH）与黑素瘤黑素皮质素MC1受体结合后的命运，因其在将细胞毒性药物或成像靶向黑素瘤方面的潜在用途而备受关注。需要诸如碘化、光亲和标记、生物素化和荧光黑素皮质素等工具来研究配体与受体相互作用过程中的命运。在本研究中，基于强效类似物[Nle4,Dphe7]α-MSH开发了一系列受体探针，并测试了它们的潜在用途。所有探针都含有核心黑素皮质素基序His-Phe-Arg-Trp。它们能轻易地与受体结合，并且似乎与内源性肽具有相似的内在效力，因此生物活性受其受体结合亲和力的调节。描述了功能性光亲和标记、生物素化和荧光探针。生物素化探针与链霉亲和素偶联时能与受体结合，尽管亲和力有所降低。
