Katahira R, Doi M, Kyogoku Y, Yamada-Nosaka A, Yamasaki K, Takai M, Kobayashi Y
International Research Laboratories, CIBA-Geigy Japan Ltd., Hyogo.
Int J Pept Protein Res. 1995 Apr;45(4):305-11. doi: 10.1111/j.1399-3011.1995.tb01042.x.
Three-dimensional structure of a human calcitonin analog (abbreviated as hCTa) in which the amino acids of the wild type are replaced at position 12, 16 and 19 by leucine residues and further at position 22 by a tyrosine residue was studied in TFE solution by 1H-NMR and distance geometry calculations. This analog has a 15-20 times activity as compared with the wild type. The amino acid replacements resulted in formation of an amphiphilic alpha-helix in the region between the residues 4-20. The overall three-dimensional structure is similar to that of the wild type. The conformational feature of hCTa with a hydrophobic face composed with a Met and four Leu residues may be related to its higher hypocalcemic potency.
通过1H-NMR和距离几何计算，在TFE溶液中研究了一种人降钙素类似物（简称为hCTa）的三维结构，其中野生型的氨基酸在第12、16和19位被亮氨酸残基取代，在第22位进一步被酪氨酸残基取代。与野生型相比，该类似物具有15至20倍的活性。氨基酸取代导致在残基4至20之间的区域形成两亲性α-螺旋。整体三维结构与野生型相似。具有由一个甲硫氨酸和四个亮氨酸残基组成的疏水表面的hCTa的构象特征可能与其较高的降血钙效力有关。
