标题：Concept of internal structural controls for evaluation of inactive synthetic peptide analogs: synthesis of [Orn13,14]apamin and its guanidination to an apamin derivative with full neurotoxic activity
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1977
卷号：74
期号：7
页码：2771-2775
DOI：10.1073/pnas.74.7.2771
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The importance of arginine residues 13 and 14 in the bee venom neurotoxin, apamin, was teste by the synthesis of replacement analogs. [13,14-di-Ndelta-trifluoroacetylornithine]Apamin was synthesized by the solid phase method on a benzhydrylamine resin. It was deprotected to [13,14-diornithine]apamin, which was then guanidinated to produce the 4-homoarginine-13,14-diarginine analog, [Har4]apamin. Neither the trifluoroacetylornithine analog nor the ornithine analog produced any detectable symptoms when injected intravenously into mice. However, the synthetic [Har4]apamin exhibited the full neurotoxic activity of native apamin and of [Har4]apamin derived from the natural toxin. This provided an internal structural control for the correctness of the primary structure of the inactive synthetic analogs and strengthened the conclusion that one, or both, of the arginine residues plays an important role in the action of apamin.
