染料-神经肽缀合物导致的受体失活。3. 染料-神经肽缀合物与庭院蜗牛和皮氏枪乌贼的FMRF酰胺受体的结合比较。

Receptor inactivation by dye-neuropeptide conjugates. 3. Comparative binding of dye-neuropeptide conjugates to FMRFamide receptors of Helix aspersa and Loligo pealei.

作者信息

Feigenbaum J J, Choubal M D, Crumrine D S, Kanofsky J R, Payza K

机构信息

Department of Research and Development, American Institute of Biotechnology, Elk Grove Village, IL 60007, USA.

出版信息

Peptides. 1996;17(8):1279-84. doi: 10.1016/s0196-9781(96)00192-1.

DOI:10.1016/s0196-9781(96)00192-1

PMID:8971919

Abstract

Three neuropeptide analogues of FMRFamide (FMRFa) were covalently attached to a tethered derivative of methylene blue to form dye-neuropeptide conjugates. The comparative binding of the latter to FMRFa receptors was subsequently examined in both Helix aspersa (circumesophageal ganglia) and squid (optic lobe membrane). In Helix, the FMRFa analogue CFMRFamide (CFMRFa) inhibited the specific binding of the FMRFa ligand [125I]daYFnLRFa in a dose-dependent manner. Az-CFMRFa, one of the dye-neuropeptide conjugates, also dose-dependently inhibited the specific binding of [125I]daYFnLRFa. Moreover, their potencies equaled or exceeded that of FMRFamide. In squid, the binding of CFMRFa and FMRFa was similar. However, the dye-neuropeptide conjugate (IC50 of 14 nM) was about 44-fold less potent than FMRFa. The conjugates were synthesized as part of a study seeking to target and inactivate preselected receptors with heretofore unattainable selectivity and permanence.

摘要

将三种FMRF酰胺（FMRFa）的神经肽类似物共价连接到亚甲蓝的连接衍生物上，形成染料-神经肽缀合物。随后在欧洲大蜗牛（围食管神经节）和鱿鱼（视叶膜）中检测了后者与FMRFa受体的相对结合情况。在欧洲大蜗牛中，FMRFa类似物CFMRF酰胺（CFMRFa）以剂量依赖性方式抑制FMRFa配体[125I]daYFnLRFa的特异性结合。染料-神经肽缀合物之一的Az-CFMRFa也以剂量依赖性方式抑制[125I]daYFnLRFa的特异性结合。此外，它们的效力等于或超过FMRF酰胺。在鱿鱼中，CFMRFa和FMRFa的结合情况相似。然而，染料-神经肽缀合物（IC50为14 nM）的效力比FMRFa低约44倍。这些缀合物是作为一项研究的一部分合成的，该研究旨在以迄今无法实现的选择性和持久性靶向并灭活预选的受体。