Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095, United States.
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92092, United States.
Inorg Chem. 2021 Apr 5;60(7):5054-5062. doi: 10.1021/acs.inorgchem.1c00087. Epub 2021 Mar 19.
Organometallic complexes have recently gained attention as competent bioconjugation reagents capable of introducing a diverse array of substrates to biomolecule substrates. Here, we detail the synthesis and characterization of an aminophosphine-supported Au(III) platform that provides rapid and convenient access to a wide array of peptide-based assemblies via cysteine -arylation. This strategy results in the formation of robust C-S covalent linkages and is an attractive method for the modification of complex biomolecules due to the high functional group tolerance, chemoselectivity, and rapid reaction kinetics associated with these arylation reactions. This work expands upon existing metal-mediated cysteine arylation by introducing a class of air-stable organometallic complexes that serve as robust bioconjugation reagents enabling the synthesis of conjugates of higher structural complexity including macrocyclic stapled and bicyclic peptides as well as a peptide-functionalized multivalent hybrid nanocluster. This organometallic-based approach provides a convenient, one-step method of peptide functionalization and macrocyclization, and has the potential to contribute to efforts directed toward developing efficient synthetic strategies of building new and diverse hybrid peptide-based assemblies.
金属有机配合物作为有能力的生物共轭试剂，能够将各种不同的底物引入生物分子底物，最近引起了人们的关注。在这里，我们详细介绍了一种氨基膦支持的 Au(III) 平台的合成和表征，该平台通过半胱氨酸芳基化，为广泛的基于肽的组装体提供了快速便捷的途径。该策略导致形成了稳定的 C-S 共价键，并且由于与这些芳基化反应相关的高官能团耐受性、化学选择性和快速反应动力学，是修饰复杂生物分子的一种有吸引力的方法。这项工作通过引入一类空气稳定的金属有机配合物扩展了现有的金属介导的半胱氨酸芳基化，这些配合物作为强大的生物偶联试剂，能够合成结构更复杂的缀合物，包括大环订书钉和双环肽以及肽功能化的多价混合纳米团簇。这种基于金属有机的方法提供了一种方便的一步法肽官能化和环化方法，并且有可能有助于开发用于构建新型和多样化的混合肽基组装体的有效合成策略。
