Metallo-Organozymes with Specific Proteolytic Activity

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

doi:10.1002/chem.201803666

Metallo-Organozymes with Specific Proteolytic Activity

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

^*Corresponding author af dette arbejde

Kemisk Institut

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.

Originalsprog	Engelsk
Tidsskrift	Chemistry - A European Journal
Vol/bind	24
Udgave nummer	66
Sider (fra-til)	17424-17428
Antal sider	5
ISSN	0947-6539
DOI	https://doi.org/10.1002/chem.201803666
Status	Udgivet - 27 nov. 2018

Adgang til dokumentet

10.1002/chem.201803666

Citationsformater

@article{6fc384bff71b40d5bf703460bfa5d34a,

title = "Metallo-Organozymes with Specific Proteolytic Activity",

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.",

author = "Embaby, {Ahmed M.} and Lelieveldt, {Lianne P. W. M.} and Frederik Diness and Morten Meldal",

year = "2018",

month = nov,

day = "27",

doi = "10.1002/chem.201803666",

language = "English",

volume = "24",

pages = "17424--17428",

journal = "Chemistry - A European Journal",

issn = "0947-6539",

publisher = "Wiley - V C H Verlag GmbH & Co. KGaA",

number = "66",

}

TY - JOUR

T1 - Metallo-Organozymes with Specific Proteolytic Activity

AU - Embaby, Ahmed M.

AU - Lelieveldt, Lianne P. W. M.

AU - Diness, Frederik

AU - Meldal, Morten

PY - 2018/11/27

Y1 - 2018/11/27

N2 - 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.

AB - 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.

U2 - 10.1002/chem.201803666

DO - 10.1002/chem.201803666

M3 - Journal article

C2 - 30146681

SN - 0947-6539

VL - 24

SP - 17424

EP - 17428

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

IS - 66

ER -

Metallo-Organozymes with Specific Proteolytic Activity

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater