Opendata, web and dolomites

LIsTEN SIGNED

β-Lactams as flaviviral NS3 protease inhibitors

Total Cost €

0

EC-Contrib. €

0

Partnership

0

Views

0

 LIsTEN project word cloud

Explore the words cloud of the LIsTEN project. It provides you a very rough idea of what is the project "LIsTEN" about.

bond    site    natural    cell    adriatic    permeability    sub    enzyme    wnv    west    moment    threat    strategy    incorporation    outbreak    climate    lactams    zika    mediterranean    nile    flaviviral    near    assays    synthesized    amino    inhibitory    acids    parts    asia    zikv    improvement    compounds    moderate    possibility    electrophilic    protease    peptide    emerged    people    denv    lactam    consequence    moiety    unnatural    warheads    living    reduce    potency    group    agents    global    exist    regions    tropical    stability    metabolic    america    valuable    billion    culture    medical    ameliorate    warming    infections    host    act    serine    active    coast    covalent    inhibitor    warhead    united    diseases    accordingly    selectivity    derivatives    residue    affinity    coupled    beta    spread    previously    membrane    consist    significantly    biochemical    virus    off    treatment    potent    replication    ns3    dengue    disease    binding    catalytic    inhibitors    purpose   

Project "LIsTEN" data sheet

The following table provides information about the project.

Coordinator
RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG 

Organization address
address: SEMINARSTRASSE 2
city: HEIDELBERG
postcode: 69117
website: www.uni-heidelberg.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Project website https://www.ipmb.uni-heidelberg.de/chemie/klein/drazic.html
 Total cost 171˙460 €
 EC max contribution 171˙460 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2016
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2017
 Duration (year-month-day) from 2017-05-02   to  2019-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG DE (HEIDELBERG) coordinator 171˙460.00

Map

 Project objective

Flaviviral infections already represent a threat to 2.5 billion people living in tropical and sub-tropical regions. As a consequence of climate change and global warming in the near future these infections are expected to spread to areas with moderate climate and the possibility of disease outbreak will exist in Europe, especially around the Mediterranean and Adriatic coast, as well as in the United States of America and large parts of Asia. At the moment no medical treatment against flaviviral diseases is available. Recently, peptide-based compounds which act as flaviviral NS3 protease inhibitors, emerged as potent agents against dengue virus (DENV), Zika virus (ZIKV) and West Nile virus (WNV). These compounds consist of two to four natural or unnatural amino acids and act by binding to the active site of the protease. Accordingly, the incorporation of an electrophilic warhead, a moiety which would facilitate the covalent binding of the inhibitor to the catalytic serine residue, into the peptide inhibitor represents a valuable strategy for the improvement of potency of such inhibitors. The goal of the proposed project is to investigate the potential of β-lactams as electrophilic warheads in DENV, ZIKV and WNV protease inhibitors. For that purpose, new β-lactam derivatives will be synthesized, coupled to peptide inhibitors previously developed by the host group and their affinity to the target will be evaluated by biochemical assays. The most potent compounds will be characterized in more detail and their activity against dengue virus replication in cell culture, off-target binding, membrane permeability and metabolic stability will be studied. We expect the formation of a covalent bond between inhibitor and active site of the enzyme to significantly improve inhibitory activity by increasing binding affinity, as well as to ameliorate selectivity and reduce off-target binding.

 Publications

year authors and title journal last update
List of publications.
2019 Tonko Dražić, Sara Kopf, James Corridan, Mila M. Leuthold, Branimir Bertoša, Christian D. Klein
Peptide-β-lactam Inhibitors of Dengue and West Nile Virus NS2B-NS3 Protease Display Two Distinct Binding Modes
published pages: 140-156, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.9b00759
Journal of Medicinal Chemistry 63/1 2020-02-12

Are you the coordinator (or a participant) of this project? Plaese send me more information about the "LISTEN" project.

For instance: the website url (it has not provided by EU-opendata yet), the logo, a more detailed description of the project (in plain text as a rtf file or a word file), some pictures (as picture files, not embedded into any word file), twitter account, linkedin page, etc.

Send me an  email (fabio@fabiodisconzi.com) and I put them in your project's page as son as possible.

Thanks. And then put a link of this page into your project's website.

The information about "LISTEN" are provided by the European Opendata Portal: CORDIS opendata.

More projects from the same programme (H2020-EU.1.3.2.)

MathematicsAnalogies (2019)

Mathematics Analogies

Read More  

MBL-Fermions (2020)

Probing many-body localization dynamics using ultracold fermions in an optical lattice

Read More  

Self-EsteemProcesses (2020)

A self-esteem process framework of the transition to work

Read More