date: 2024-06-12T11:00:14Z
pdf:unmappedUnicodeCharsPerPage: 0
pdf:PDFVersion: 1.7
pdf:docinfo:title: Substitution-Induced Mechanistic Switching in SNAr-Warheads for Cysteine Proteases
xmp:CreatorTool: LaTeX with hyperref
Keywords: electrophilic warhead; SNAr; rhodesain; covalency; reversibility; permeability
access_permission:modify_annotations: true
access_permission:can_print_degraded: true
subject: The aim of this study was to investigate the transition from non-covalent reversible over covalent reversible to covalent irreversible inhibition of cysteine proteases by making delicate structural changes to the warhead scaffold. To this end, dipeptidic rhodesain inhibitors with different N-terminal electrophilic arenes as warheads relying on the SNAr mechanism were synthesized and investigated. Strong structure?activity relationships of the inhibition potency, the degree of covalency, and the reversibility of binding on the arene substitution pattern were found. The studies were complemented and substantiated by molecular docking and quantum-mechanical calculations of model systems. Furthermore, the improvement in the membrane permeability of peptide esters in comparison to their corresponding carboxylic acids was exemplified.
dc:creator: Collin Zimmer, Jan Brauer, Dorota Ferenc, Jessica Meyr, Patrick Müller, Hans-Joachim Räder, Bernd Engels, Till Opatz and Tanja Schirmeister
dcterms:created: 2024-06-12T10:57:22Z
Last-Modified: 2024-06-12T11:00:14Z
dcterms:modified: 2024-06-12T11:00:14Z
dc:format: application/pdf; version=1.7
title: Substitution-Induced Mechanistic Switching in SNAr-Warheads for Cysteine Proteases
Last-Save-Date: 2024-06-12T11:00:14Z
pdf:docinfo:creator_tool: LaTeX with hyperref
access_permission:fill_in_form: true
pdf:docinfo:keywords: electrophilic warhead; SNAr; rhodesain; covalency; reversibility; permeability
pdf:docinfo:modified: 2024-06-12T11:00:14Z
meta:save-date: 2024-06-12T11:00:14Z
pdf:encrypted: false
dc:title: Substitution-Induced Mechanistic Switching in SNAr-Warheads for Cysteine Proteases
modified: 2024-06-12T11:00:14Z
cp:subject: The aim of this study was to investigate the transition from non-covalent reversible over covalent reversible to covalent irreversible inhibition of cysteine proteases by making delicate structural changes to the warhead scaffold. To this end, dipeptidic rhodesain inhibitors with different N-terminal electrophilic arenes as warheads relying on the SNAr mechanism were synthesized and investigated. Strong structure?activity relationships of the inhibition potency, the degree of covalency, and the reversibility of binding on the arene substitution pattern were found. The studies were complemented and substantiated by molecular docking and quantum-mechanical calculations of model systems. Furthermore, the improvement in the membrane permeability of peptide esters in comparison to their corresponding carboxylic acids was exemplified.
pdf:docinfo:subject: The aim of this study was to investigate the transition from non-covalent reversible over covalent reversible to covalent irreversible inhibition of cysteine proteases by making delicate structural changes to the warhead scaffold. To this end, dipeptidic rhodesain inhibitors with different N-terminal electrophilic arenes as warheads relying on the SNAr mechanism were synthesized and investigated. Strong structure?activity relationships of the inhibition potency, the degree of covalency, and the reversibility of binding on the arene substitution pattern were found. The studies were complemented and substantiated by molecular docking and quantum-mechanical calculations of model systems. Furthermore, the improvement in the membrane permeability of peptide esters in comparison to their corresponding carboxylic acids was exemplified.
Content-Type: application/pdf
pdf:docinfo:creator: Collin Zimmer, Jan Brauer, Dorota Ferenc, Jessica Meyr, Patrick Müller, Hans-Joachim Räder, Bernd Engels, Till Opatz and Tanja Schirmeister
X-Parsed-By: org.apache.tika.parser.DefaultParser
creator: Collin Zimmer, Jan Brauer, Dorota Ferenc, Jessica Meyr, Patrick Müller, Hans-Joachim Räder, Bernd Engels, Till Opatz and Tanja Schirmeister
meta:author: Collin Zimmer, Jan Brauer, Dorota Ferenc, Jessica Meyr, Patrick Müller, Hans-Joachim Räder, Bernd Engels, Till Opatz and Tanja Schirmeister
dc:subject: electrophilic warhead; SNAr; rhodesain; covalency; reversibility; permeability
meta:creation-date: 2024-06-12T10:57:22Z
created: 2024-06-12T10:57:22Z
access_permission:extract_for_accessibility: true
access_permission:assemble_document: true
xmpTPg:NPages: 16
Creation-Date: 2024-06-12T10:57:22Z
pdf:charsPerPage: 3837
access_permission:extract_content: true
access_permission:can_print: true
meta:keyword: electrophilic warhead; SNAr; rhodesain; covalency; reversibility; permeability
Author: Collin Zimmer, Jan Brauer, Dorota Ferenc, Jessica Meyr, Patrick Müller, Hans-Joachim Räder, Bernd Engels, Till Opatz and Tanja Schirmeister
producer: pdfTeX-1.40.25
access_permission:can_modify: true
pdf:docinfo:producer: pdfTeX-1.40.25
pdf:docinfo:created: 2024-06-12T10:57:22Z