Gold compounds have emerged as a novel class of metallodrugs with a promising future in medicinal inorganic chemistry. Despite gold compounds have been intensively investigated for the treatment of many diseases, their mechanism of action is not fully understood at the molecular level. However, the recognition process by proteins is accepted as a key feature for the biological activity of these molecules. This review presents the research performed during the last decade(s) concerning the structural studies on the products of the reactions between gold-based drugs and proteins. A comparative analysis of the structural features of the known gold/protein adducts suggests that several binding mechanisms are possible. It emerges that gold(III) compounds break down before or upon protein binding and that Au(III) reduces to Au(I) during this process. In agreement with the hard and soft acids and bases (HSAB) theory, Au(I) centers prefer thiolates of free Cys side chains; sulfur atoms of Met are less frequently observed, while N atoms of the side chains of His, Lys, Arg and Gln and O atoms of Glu and Asp are also possible Au binding sites. Au can bridge two protein residue side chains (Cys/Cys, Cys/His, Cys/Asp, Cys/Asn, His/His, His/Lys, His/Gln); Au…π interactions can also be formed. The formation of gold/protein adducts does not alter the overall folding of the investigated proteins, but it can modify the active site conformation, inhibiting the enzymatic activity. The process of gold metalation of proteins is selective.

金化合物已成为一类新型的金属药物，在药用无机化学中具有广阔的前景。尽管已经对金化合物进行了广泛的研究以治疗许多疾病，但在分子水平上尚未完全理解其作用机理。然而，蛋白质的识别过程被认为是这些分子生物学活性的关键特征。这篇综述介绍了过去十年间有关金基药物与蛋白质之间反应产物的结构研究的研究。对已知的金/蛋白质加合物的结构特征的比较分析表明，几种结合机制是可能的。结果表明，金（III）化合物在蛋白质结合之前或之后分解，并且在此过程中Au（III）还原为Au（I）。与硬酸和软酸和碱（HSAB）理论一致，Au（I）中心更喜欢游离Cys侧链的硫醇盐。Met的硫原子较少见，而His，Lys，Arg和Gln的侧链的N原子以及Glu和Asp的O原子也可能是Au结合位点。Au可以桥接两个蛋白质残基侧链（Cys / Cys，Cys / His，Cys / Asp，Cys / Asn，His / His，His / Lys，His / Gln）；也可以形成Au…π相互作用。金/蛋白质加合物的形成不会改变所研究蛋白质的整体折叠，但可以修饰活性位点构象，从而抑制酶的活性。蛋白质的金金属化过程是选择性的。而His，Lys，Arg和Gln的侧链的N原子和Glu和Asp的O原子也可能是Au结合位点。Au可以桥接两个蛋白质残基侧链（Cys / Cys，Cys / His，Cys / Asp，Cys / Asn，His / His，His / Lys，His / Gln）；也可以形成Au…π相互作用。金/蛋白质加合物的形成不会改变所研究蛋白质的整体折叠，但可以修饰活性位点构象，从而抑制酶的活性。蛋白质的金金属化过程是选择性的。而His，Lys，Arg和Gln的侧链的N原子和Glu和Asp的O原子也可能是Au结合位点。Au可以桥接两个蛋白质残基侧链（Cys / Cys，Cys / His，Cys / Asp，Cys / Asn，His / His，His / Lys，His / Gln）；也可以形成Au…π相互作用。金/蛋白质加合物的形成不会改变所研究蛋白质的整体折叠，但可以修饰活性位点构象，从而抑制酶的活性。蛋白质的金金属化过程是选择性的。金/蛋白质加合物的形成不会改变所研究蛋白质的整体折叠，但可以修饰活性位点构象，从而抑制酶的活性。蛋白质的金金属化过程是选择性的。金/蛋白质加合物的形成不会改变所研究蛋白质的整体折叠，但可以修饰活性位点构象，从而抑制酶的活性。蛋白质的金金属化过程是选择性的。