Covalent and non-covalent albumin binding of Au(i) bis-NHCsviapost-synthetic amide modification

Abstract

Au(i) bis-N-heterocyclic carbenes (NHCs) functionalized using an amide linker were found to bind to human serum albumin (HSA) in covalent and non-covalent fashion. The solubility and in vitro anti-cancer activity of these new conjugates were studied.

Exploiting click-chemistry: backbone post-functionalisation of homoleptic gold(i) 1,2,3-triazole-5-ylidene complexes

“…26 Post-functionalisation strategies typically include biologically native functional groups. 22,23,33 While these have been reported for attaching small molecules, 17,19,22,23,33,34 we only found one example where the post-conjugation to an antibody was facilitated, however here efficacy of the resulting ADCs was hampered due to their low cytotoxicity. 10 The strain promoted azide alkyne cycloaddition (SPAAC) was established by Bertozzi et al as a reliable, selective and versatile technique for the conjugation of biomolecules and was awarded with the Nobel prize in chemistry in 2022.…”

“…15,16 To further enhance the selectivity towards cancer cells, several examples of Au( i ) NHC im complexes suitable for post-modification have been reported. They bear inter alia hydroxyl, 17–19 activated ester, 10,20 azide 21 and carboxylic acid 22,23 functional groups, which are available for further bioconjugation. The azide–alkyne cycloaddition (AAC) reaction has proven successful on both pre- and post-functionalisation of Au( i ) NHC im -complexes.…”

Chemical Conjugation in Drug Delivery Systems

“…Recently, a synthetic method to access covalently bound Bis-N-heterocyclic carbene (bis-NHC) gold(I) (Au(I) bis-NHC) with serum albumin adducts have been developed without affecting the metal center active site. The procedure can be described as a post-synthetic amide conjugation that relies on the use of the new Au(I) bisNHC complex bearing a carboxylic acid functional group (Sen et al, 2021).…”

Fluorescent Chemosensors for Ion and Molecule Recognition: The Next Chapter

“…Within this field, protein-based hybridization is an appealing strategy that exhibits ideal biocompatibility. A prominent example of this approach exploits the host-guest chemistry of human serum albumin (HSA) with highly lipophilic molecules such as cell impermeable and insoluble fluorescent probes (Sheng et al, 2014;Han et al, 2020;Jia et al, 2020;Sen et al, 2020;Sen et al, 2021).…”