Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, USA.
J Sep Sci. 2010 Aug;33(16):2506-14. doi: 10.1002/jssc.201000271.
Dynorphin A 1-17 is an endogenous neuropeptide implicated in a variety of neurological disorders including Alzheimer's and Parkinson's diseases and neuropathic pain. Metabolites of this peptide can exhibit their own unique effects in vivo, and it is possible that one of these metabolites is responsible for the neurotoxicity. In this article, the use of CE for the separation of dynorphin A 1-17 from four of its metabolites is described. Buffer additives were investigated to eliminate peptide adsorption to the capillary wall and to improve resolution between closely related metabolites. On-capillary copper complexation was employed and was shown to improve separation efficiency as compared with the separation of native peptides. The method was then applied to in vitro dynorphin metabolism in human plasma as well as rat brain and rat spinal cord slices.
强啡肽 A 1-17 是一种内源性神经肽,与多种神经紊乱相关,包括阿尔茨海默病、帕金森病和神经病理性疼痛。这种肽的代谢物在体内可以表现出自身独特的作用,而这些代谢物之一可能是造成神经毒性的原因。本文描述了使用毛细管电泳技术从其四种代谢物中分离强啡肽 A 1-17。考察了缓冲添加剂以消除肽在毛细管壁上的吸附,并改善密切相关代谢物之间的分辨率。采用了毛细管内铜络合作用,与天然肽的分离相比,提高了分离效率。该方法随后应用于人血浆、大鼠脑和大鼠脊髓切片中的体外强啡肽代谢研究。