Gottfried H, Mamikunian G, Falkmer S, Emdin S O, Landaw E, Dadourian B
Acta Paediatr Scand Suppl. 1977(270):26-36. doi: 10.1111/j.1651-2227.1977.tb15118.x.
By means of a statistical analysis of the occurrence of amino-acid residues in the polypeptide chains of several gastro-entero-pancreatic (GEP) hormones an investigation was undertaken to determine whether any of these hormones might be related to each other--possibly from an evolutionary point of view. Particular interest was paid to the occurrence of small charged segments, i.e. those with acidic or basic amino acid residues, since such segments can be presumed to play a role in hormonal receptor binding mechanisms. By this method hormonal relationships were suggested by the observation that these small charged amino-acid sequences, contained in the hormonal structures, match as a result of non-randomness. It was found that hagfish and human insulin were related on a molecular level not only to the newly discovered (avian, bovine, human) pancreatic polypeptide (PP) but also to some other GEP hormones (VIP, GIP, glucagon) as well as to calcitonin and to the alpha-subunit of the glycoprotein hormones. Interpretation of the statistical data suggests that all these peptide hormones are related by a common hexapeptide sequence which contributed, at an evolutionary point, to their molecular architecture. A hexapeptide segment of APP is statistically related to a sequence of equal size in the carboxy terminal region of the A-chain of both hagfish and human insulin, providing the first instance of their structural similarity. Correlations between PP, insulin, glucagon, VIP, and calcitonin provide a tentative basis for predicting the production of one or more of these peptide hormones by immature or de-differentiated cells of neoplasms and non-neoplastic pathologic lesions of the GEP endocrine system.
通过对几种胃肠胰（GEP）激素多肽链中氨基酸残基出现情况的统计分析，展开了一项研究，以确定这些激素之间是否可能存在相互关系——可能是从进化的角度。特别关注了小的带电片段的出现情况，即那些含有酸性或碱性氨基酸残基的片段，因为可以推测这些片段在激素受体结合机制中起作用。通过这种方法，由于观察到激素结构中包含的这些小的带电氨基酸序列因非随机性而匹配，从而提示了激素之间的关系。研究发现，盲鳗和人类胰岛素在分子水平上不仅与新发现的（鸟类、牛类、人类）胰多肽（PP）有关，还与其他一些GEP激素（血管活性肠肽、胃抑肽、胰高血糖素）以及降钙素和糖蛋白激素的α亚基有关。对统计数据的解释表明，所有这些肽类激素都通过一个共同的六肽序列相关联，该序列在进化过程中对它们的分子结构有贡献。APP的一个六肽片段在统计学上与盲鳗和人类胰岛素A链羧基末端区域中一个等长的序列相关，这是它们结构相似性的首个实例。PP、胰岛素、胰高血糖素、血管活性肠肽和降钙素之间的相关性为预测肿瘤未成熟或去分化细胞以及GEP内分泌系统的非肿瘤性病理病变产生这些肽类激素中的一种或多种提供了初步依据。
