Synergistic effects and promising anticancer activities encourage the combination of non-steroidal anti-inflammatory drugs with metallodrugs. Here, we discuss the interactions of an organometallic complex consisting of an acetylsalicylic acid (ASA) moiety attached to a Pt^II center via an alkenol linker in a Zeise’s salt-type coordination (ASA–buten–PtCl₃) with model peptides angiotensin 1 (AT), substance P (Sub P), and ubiquitin (UQ). Top-down mass spectrometry experiments show that the amino acid involved in the initial binding to the metal complex controls the coordination sphere of Pt^II in the adducts. The strong trans labilizing effect of the coordinating sulfur atom in Met causes fast release of the organic moiety and leads to the formation of dimers and oligomers in the case of Sub P. In contrast, interactions with nitrogen donors in AT result in stable adducts containing the intact ASA–buten–Pt^II complex. UQ forms two sets of Pt^II adducts, only one of them retains the ASA moiety, which is presumably the result of an unexpected binding geometry. Importantly, UQ is additionally acetylated at various Ser and Lys residues by the ASA–buten–PtCl₃ complex. Control experiments with ASA are negative. This is the first example of concomitant platination and acetylation of a peptide with an ASA metal complex.

中文翻译：

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自上而下的质谱分析揭示了带有蔡斯盐衍生物的乙酰水杨酸与肽的多重相互作用。

协同效应和有前景的抗癌活性鼓励非甾体抗炎药与金属药物的组合。^{在这里，我们讨论了由乙酰}水杨酸 (ASA) 部分组成的有机金属复合物与模型肽血管紧张素 1 ₍ AT)、P 物质 (Sub P) 和泛素 (UQ)。自上而下的质谱实验表明，参与与金属配合物初始结合的氨基酸控制着加合物中Pt ^{II的配位范围。}Met 中配位硫原子的强烈反式不稳定效应导致有机部分快速释放，并导致 Sub P 中二聚体和低聚物的形成。相反，与 AT 中的氮供体相互作用会产生含有以下成分的稳定加合物：完整的 ASA-丁烯-Pt ^II复合物。UQ 形成两组 Pt ^II加合物，其中只有一组保留 ASA 部分，这可能是意外结合几何形状的结果。重要的是，UQ 在多个 Ser 和 Lys 残基上还被 ASA-丁烯-PtCl ₃复合物乙酰化。ASA 对照实验结果为阴性。这是肽与 ASA 金属络合物同时铂化和乙酰化的第一个例子。