Biocompatibility and Therapeutic Potential of Glycosylated Albumin Artificial Metalloenzymes
Nat. Catal. 2019, 2, 780-792, 10.1038/s41929-019-0317-4
The ability of natural metalloproteins to prevent inactivation of their metal cofactors by biological metabolites, such as glutathione, is an area that has been largely ignored in the field of artificial metalloenzyme (ArM) development. Yet, for ArM research to transition into future therapeutic applications, biocompatibility remains a crucial component. The work presented here shows the creation of a human serum albumin-based ArM that can robustly protect the catalytic activity of a bound ruthenium metal, even in the presence of 20 mM glutathione under in vitro conditions. To exploit this biocompatibility, the concept of glycosylated artificial metalloenzymes (GArM) was developed, which is based on functionalizing ArMs with N-glycan targeting moieties. As a potential drug therapy, this study shows that ruthenium-bound GArM complexes could preferentially accumulate to varying cancer cell lines via glycan-based targeting for prodrug activation of the anticancer agent umbelliprenin using ring-closing metathesis.
Metal: RuLigand type: Hoveyda–GrubbsHost protein: Human serum albumin (HSA)Anchoring strategy: SupramolecularOptimization: ChemicalReaction: Ring closing metathesisMax TON: 29.9ee: ---PDB: ---Notes: ---