Kotuniak Radosław, Frączyk Tomasz, Skrobecki Piotr, Płonka Dawid, Bal Wojciech
Institute of Biochemistry and Biophysics , Polish Academy of Sciences , Pawińskiego 5a , 02-106 Warsaw , Poland.
Department of Immunology, Transplantology and Internal Medicine , Medical University of Warsaw , Nowogrodzka 59 , 02-006 Warsaw , Poland.
Inorg Chem. 2018 Dec 17;57(24):15507-15516. doi: 10.1021/acs.inorgchem.8b02841. Epub 2018 Nov 27.
The Cu(II) and Zn(II) binding abilities of Gly-His-Thr-Asp-amide (GHTD-am), a tetrapeptide coreleased from the pancreas along with insulin, were studied using UV-vis and circular dichroism spectroscopies, potentiometry, and calorimetry. GHTD-am is a very strong Cu(II) chelator, forming a three-nitrogen complex with a conditional affinity constant K at pH 7.4 of 4.5 × 10 M. The fourth coordination site can be occupied by a solvent molecule or a ternary ligand, such as imidazole, with K on the order of several hundred reciprocal molar. The Zn(II) binding ability of GHTD-am is relatively weak, with K values at pH 7.4 of 3.0 × 10 and 2.0 × 10 M for the first and second GHTD-am molecule coordinated, respectively. These results are discussed in light of the modes of interactions of Zn(II) and Cu(II) ions with insulin. A direct effect of GHTD-am on the Zn(II) interactions with insulin is unlikely, but its Cu(II) complex may have a biological relevance because of its high affinity and ability to form ternary complexes.
利用紫外可见光谱、圆二色光谱、电位滴定法和量热法，研究了与胰岛素一起从胰腺中共同释放的四肽甘氨酰-组氨酰-苏氨酰-天冬酰胺（GHTD-am）与铜（II）和锌（II）的结合能力。GHTD-am是一种非常强的铜（II）螯合剂，在pH 7.4时形成一种三氮配合物，其条件亲和常数K为4.5×10 M。第四个配位位点可被溶剂分子或三元配体（如咪唑）占据，其K值约为几百倒数摩尔。GHTD-am与锌（II）的结合能力相对较弱，在pH 7.4时，第一个和第二个配位的GHTD-am分子的K值分别为3.0×10和2.0×10 M。根据锌（II）和铜（II）离子与胰岛素的相互作用模式对这些结果进行了讨论。GHTD-am对锌（II）与胰岛素相互作用的直接影响不太可能，但由于其高亲和力和形成三元配合物的能力，其铜（II）配合物可能具有生物学相关性。
