Kadej Agnieszka, Kuczer Mariola, Czarniewska Elżbieta, Urbański Arkadiusz, Rosiński Grzegorz, Kowalik-Jankowska Teresa
Faculty of Chemistry, University of Wrocław, Joliot-Curie 14, 50-383 Wrocław, Poland.
Department of Animal Physiology and Development, Institute of Experimental Biology, Adam Mickiewicz University, Umultowska 89, 61-614 Poznań, Poland.
J Inorg Biochem. 2016 Oct;163:147-161. doi: 10.1016/j.jinorgbio.2016.07.006. Epub 2016 Jul 9.
Copper(II) complex formation processes between the alloferon 1 (Allo1) (HGVSGHGQHGVHG) analogues where the tryptophan residue is introducing in the place His residue H1W, H6W, H9W and H12W have been studied by potentiometric, UV-visible, CD and EPR spectroscopic, and MS methods. For all analogues of alloferon 1 complex speciation have been obtained for a 1:1 metal-to-ligand molar ratio and 2:1 of H1W because of precipitation at higher (2:1, 3:1 and 4:1) ratios. At physiological pH7.4 and a 1:1 metal-to-ligand molar ratio the tryptophan analogues of alloferon 1 form the CuHL and/or CuHL complexes with the 4N binding mode. The introduction of tryptophan in place of histidine residues changes the distribution diagram of the complexes formed with the change of pH and their stability constants compared to the respective substituted alanine analogues of alloferon 1. The CuHL, CuHL and CuHL complexes of the tryptophan analogues are more stable from 1 to 5 log units in comparison to those of the alanine analogues. This stabilization of the complexes may result from cation(Cu(II))-π and indole/imidazole ring interactions. The induction of apoptosis in vivo, in Tenebrio molitor cells by the ligands and their copper(II) complexes at pH7.4 was studied. The biological results show that copper(II) ions in vivo did not cause any apparent apoptotic features. The most active were the H12W peptide and Cu(II)-H12W complex formed at pH7.4.
已通过电位滴定法、紫外可见光谱法、圆二色光谱法、电子顺磁共振光谱法和质谱法研究了别洛干扰素1（Allo1）（HGVSGHGQHGVHG）类似物与铜（II）的络合形成过程，这些类似物中色氨酸残基取代了组氨酸残基，分别为H1W、H6W、H9W和H12W。对于别洛干扰素1的所有类似物，在金属与配体摩尔比为1:1时获得了络合物的物种形成情况，而对于H1W，在2:1时由于在更高比例（2:1、3:1和4:1）下会沉淀，所以只得到了2:1的情况。在生理pH 7.4和金属与配体摩尔比为1:1时，别洛干扰素1的色氨酸类似物以4N结合模式形成CuHL和/或CuHL络合物。与别洛干扰素1相应的取代丙氨酸类似物相比，用色氨酸取代组氨酸残基会改变形成的络合物的分布图以及其稳定性常数随pH的变化。色氨酸类似物的CuHL、CuHL和CuHL络合物比丙氨酸类似物的络合物稳定1至5个对数单位。这种络合物的稳定性可能源于阳离子（Cu（II））-π和吲哚/咪唑环相互作用。研究了在pH 7.4时配体及其铜（II）络合物在黄粉虫细胞中体内诱导凋亡的情况。生物学结果表明，体内的铜（II）离子未引起任何明显的凋亡特征。最具活性的是在pH 7.4时形成的H12W肽和Cu（II）-H12W络合物。
