On-Bead Screening of a Combinatorial Fumaric Acid Derived Peptide Library Yields Antiplasmodial Cysteine Protease Inhibitors with Unusual Peptide Sequences

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • Uwe Machon
  • Christian Ruchold
  • Martin Stempka
  • Tanja Schirmeister
  • Christoph Gelhaus
  • Matthias Leippe
  • Jiri Gut
  • Philip J Rosenthal
  • Caroline Kisker
  • Matthias Leyh
  • Carsten Schmuck
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000269746600013&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1021/jm900629w
eISSN
1520-4804
Externe Identifier
  • Clarivate Analytics Document Solution ID: 493OJ
  • PubMed Identifier: 19715342
ISSN
0022-2623
Ausgabe der Veröffentlichung
18
Zeitschrift
JOURNAL OF MEDICINAL CHEMISTRY
Paginierung
5662 - 5672
Datum der Veröffentlichung
2009
Status
Published
Titel
On-Bead Screening of a Combinatorial Fumaric Acid Derived Peptide Library Yields Antiplasmodial Cysteine Protease Inhibitors with Unusual Peptide Sequences
Sub types
  • Article
Ausgabe der Zeitschrift
52

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:
Autoren
  • Uwe Machon
  • Christian Büchold
  • Martin Stempka
  • Tanja Schirmeister
  • Christoph Gelhaus
  • Matthias Leippe
  • Jiri Gut
  • Philip J Rosenthal
  • Caroline Kisker
  • Matthias Leyh
  • Carsten Schmuck
DOI
10.1021/jm900629w
eISSN
1520-4804
ISSN
0022-2623
Ausgabe der Veröffentlichung
18
Zeitschrift
Journal of Medicinal Chemistry
Sprache
en
Online publication date
2009
Paginierung
5662 - 5672
Datum der Veröffentlichung
2009
Status
Published
Herausgeber
American Chemical Society (ACS)
Herausgeber URL
http://dx.doi.org/10.1021/jm900629w
Datum der Datenerfassung
2023
Titel
On-Bead Screening of a Combinatorial Fumaric Acid Derived Peptide Library Yields Antiplasmodial Cysteine Protease Inhibitors with Unusual Peptide Sequences
Ausgabe der Zeitschrift
52

Datenquelle: Crossref

Abstract
A new class of cysteine protease inhibitors based on fumaric acid derived oligopeptides was successfully identified from a high-throughput screening of a solid-phase bound combinatorial library. As target enzymes falcipain and rhodesain were used, which play important roles in the life cycles of the parasites which cause malaria (Plasmodium falciparum) and African sleeping sickness (Trypanosoma brucei rhodesiense). The best inhibitors with unusual amino acid sequences not reported before for this type of enzyme were also fully analyzed in detail in solution. K(i) values in the lower micromolar and even nanomolar region were found. Some inhibitors are even active against plasmodia and show good selectivity relative to other enzymes. Also the mechanism of action was studied and could be shown to be irreversible inhibition.
Addresses
  • Institute of Organic Chemistry, University of Duisburg-Essen, Universitatstrasse 7, 45141 Essen, Germany.
Autoren
  • Uwe Machon
  • Christian Büchold
  • Martin Stempka
  • Tanja Schirmeister
  • Christoph Gelhaus
  • Matthias Leippe
  • Jiri Gut
  • Philip J Rosenthal
  • Caroline Kisker
  • Matthias Leyh
  • Carsten Schmuck
DOI
10.1021/jm900629w
eISSN
1520-4804
Externe Identifier
  • PubMed Identifier: 19715342
Open access
false
ISSN
0022-2623
Ausgabe der Veröffentlichung
18
Zeitschrift
Journal of medicinal chemistry
Schlüsselwörter
  • Animals
  • Cattle
  • Humans
  • Plasmodium falciparum
  • Diamide
  • Fumarates
  • Cathepsins
  • Cysteine Endopeptidases
  • Peptide Library
  • Cysteine Proteinase Inhibitors
  • Antiprotozoal Agents
  • Combinatorial Chemistry Techniques
  • Drug Evaluation, Preclinical
  • Amino Acid Sequence
  • Cathepsin L
Sprache
eng
Medium
Print
Paginierung
5662 - 5672
Datum der Veröffentlichung
2009
Status
Published
Datum der Datenerfassung
2009
Titel
On-bead screening of a combinatorial fumaric acid derived peptide library yields antiplasmodial cysteine protease inhibitors with unusual peptide sequences.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
52

Datenquelle: Europe PubMed Central

Abstract
A new class of cysteine protease inhibitors based on fumaric acid derived oligopeptides was successfully identified from a high-throughput screening of a solid-phase bound combinatorial library. As target enzymes falcipain and rhodesain were used, which play important roles in the life cycles of the parasites which cause malaria (Plasmodium falciparum) and African sleeping sickness (Trypanosoma brucei rhodesiense). The best inhibitors with unusual amino acid sequences not reported before for this type of enzyme were also fully analyzed in detail in solution. K(i) values in the lower micromolar and even nanomolar region were found. Some inhibitors are even active against plasmodia and show good selectivity relative to other enzymes. Also the mechanism of action was studied and could be shown to be irreversible inhibition.
Autoren
  • Uwe Machon
  • Christian Büchold
  • Martin Stempka
  • Tanja Schirmeister
  • Christoph Gelhaus
  • Matthias Leippe
  • Jiri Gut
  • Philip J Rosenthal
  • Caroline Kisker
  • Matthias Leyh
  • Carsten Schmuck
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/19715342
DOI
10.1021/jm900629w
eISSN
1520-4804
Ausgabe der Veröffentlichung
18
Zeitschrift
J Med Chem
Schlüsselwörter
  • Amino Acid Sequence
  • Animals
  • Antiprotozoal Agents
  • Cathepsin L
  • Cathepsins
  • Cattle
  • Combinatorial Chemistry Techniques
  • Cysteine Endopeptidases
  • Cysteine Proteinase Inhibitors
  • Diamide
  • Drug Evaluation, Preclinical
  • Fumarates
  • Humans
  • Peptide Library
  • Plasmodium falciparum
Sprache
eng
Country
United States
Paginierung
5662 - 5672
Datum der Veröffentlichung
2009
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2009
Titel
On-bead screening of a combinatorial fumaric acid derived peptide library yields antiplasmodial cysteine protease inhibitors with unusual peptide sequences.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
52

Datenquelle: PubMed

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