Folkers K, Chang D, Humphries J, Carraway R, Leeman S E, Bowers C Y
Proc Natl Acad Sci U S A. 1976 Nov;73(11):3833-7. doi: 10.1073/pnas.73.11.3833.
It was considered, a priori, that the isolation of the tridecapeptide, neurotensin, might have inadvertently sllowed the hydrolysis of either the [Gln4]- or the [Leu13-NH2]-moieties. Neurotensin and its three acid and amide analogs, i.e., [Gln4]-neurotensin, neurotensin-NH2, and [Gln4]-neurotensin-NH2 were synthesized. Neurotensin and [Gln4]-neurotensin were indistinguishable by the hypotensive assay, hyperglycemic assay, contraction of the ileum, and radioimmunoassay. Neurotensin-NH2 and [Gln4]-neurotensin-NH2 showed less than 1% of these neurotensin activities. Present information does not elucidate whether the glutamic acid residue in position 4 of neurotensin in situ is present as Glu4 or as Gln4. At high levels, neurotensin released the luteinizing hormone, follicle stimulating hormone, and thyrotropin; [Gln4]-neurotensin-NH2 released thyrotropin, and [Gln4]-neurotensin released luteinizing hormone and follicle stimulating hormone, but these activities do not appear biologically significant.
先验地认为，十三肽神经降压素的分离可能无意中导致了[Gln4] - 或[Leu13 - NH2] - 部分的水解。合成了神经降压素及其三种酸和酰胺类似物，即[Gln4] - 神经降压素、神经降压素 - NH2和[Gln4] - 神经降压素 - NH2。通过降压试验、高血糖试验、回肠收缩试验和放射免疫测定法，神经降压素和[Gln4] - 神经降压素无法区分。神经降压素 - NH2和[Gln4] - 神经降压素 - NH2的这些神经降压素活性不到1%。目前的信息并未阐明神经降压素第4位的谷氨酸残基在原位是以Glu4还是Gln4的形式存在。在高剂量时，神经降压素释放促黄体生成素、促卵泡生成素和促甲状腺激素；[Gln4] - 神经降压素 - NH2释放促甲状腺激素，[Gln4] - 神经降压素释放促黄体生成素和促卵泡生成素，但这些活性在生物学上似乎并不显著。
