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Metallo‐Organozymes with Specific Proteolytic Activity
Author(s) -
Embaby Ahmed M.,
Lelieveldt Lianne P. W. M.,
Diness Frederik,
Meldal Morten
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201803666
Subject(s) - peptide , cleave , cleavage (geology) , chemistry , combinatorial chemistry , peptide bond , selectivity , förster resonance energy transfer , stereochemistry , biochemistry , catalysis , enzyme , biology , fluorescence , paleontology , physics , quantum mechanics , fracture (geology)
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.