Metallo-Organozymes with Specific Proteolytic Activity

Ahmed M. Embaby, Lianne P. W. M. Lelieveldt, Frederik Diness, Morten Meldal*

*Corresponding author for this work

Abstract

Metallopeptides that show efficiency and selectivity in peptide bond cleavage in water at room temperature and neutral conditions are presented. These small and versatile organozymes take advantage of metal-coordinating building blocks that are strategically positioned centrally in a peptide backbone or in a peptide macrocycle. This approach provided peptide–metal complexes with scaffolds capable of utilizing the peptide functionality for productive binding of fluorogenic FRET peptide substrates, subsequently leading to highly selective peptide bond cleavage. The ligand chemistry has been optimized to provide an easy access to new metallo-peptides with the ability to cleave previously inaccessible peptide bonds. Evolutionary principles of stepwise selection and variation offered by combinatorial methods were used and were guided by molecular modeling to develop catalytic metallo-peptides that mimic metalloproteases.

Original languageEnglish
JournalChemistry - A European Journal
Volume24
Issue number66
Pages (from-to)17424-17428
Number of pages5
ISSN0947-6539
DOIs
Publication statusPublished - 27 Nov 2018

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