alexa Targeting Trypanosoma Brucei FPPs By Fragment- Based Drug Discovery
ISSN: 0974-276X

Journal of Proteomics & Bioinformatics
Open Access

Like us on:
OMICS International organises 3000+ Global Conferenceseries Events every year across USA, Europe & Asia with support from 1000 more scientific Societies and Publishes 700+ Open Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.

Open Access Journals gaining more Readers and Citations

700 Journals and 15,000,000 Readers Each Journal is getting 25,000+ Readers

This Readership is 10 times more when compared to other Subscription Journals (Source: Google Analytics)

Share This Page

Additional Info

Loading
Loading Please wait..
 

9th International Conference on Structural Biology
September 18-20, 2017 Zurich, Switzerland

Lena Muenzker, Joy Petrick, Gerhard Klebe, Andreas Marzinzik and Wolfgang Jahnke
Novartis Institutes for Biomedical Research, Switzerland
Philipps University of Marburg, Germany
Posters & Accepted Abstracts: J Proteomics Bioinform
DOI: 10.4172/0974-276X-C1-101
Abstract
Trypanosoma brucei is the causative agent of Human African Trypanosomiasis (HAT), one of the most neglected diseases with only limited medication options for treatment. Therefore, new drugs with a better safety and efficiency profile for the two stages of the disease are highly demanded. Nitrogen-containing bisphosphonates have demonstrated anti-parasite activity. They inhibit farnesyl pyrophosphate synthase (FPPS) and are in clinical use for bone diseases. They are also investigated for a broader application, such as antitumor or antiparasitic agents. However, due to their pharmacokinetic properties, alternative chemotypes are highly desired. Previous efforts at Novartis have identified an allosteric pocket on human FPPS by a fragment based approach, and a similar pocket also exists in T. brucei FPPS. The combination of these results laid the foundation of this work. In the first step, T. brucei FPPS protein was subjected to an NMR fragment screen using 1H, water-LOGSY and T1rho NMR experiments. Mixtures of eight compounds were screened, and fragments fulfilling hit criteria were followed up in single compound NMR experiments. We further validated fragment hits in protein-observed 2D-NMR experiments and estimated Kd values by NMR. Additionally, we investigated fragment binding on T. cruzi and human FPPS to enable selectivity studies and the comparison of results. This approach identified 25 diverse fragment hits for T. brucei FPPS, which were subjected to crystallization experiments to identify the exact binding location and binding mode. In summary, we demonstrated the application of a fragment-based approach for the identification of T. brucei FPPS binding compounds and further want to drive the drug discovery process from initial fragment hits to tool compounds with high binding affinity that inhibit the FPPS enzyme function selectively and interfere the parasitic growth.
Biography

Lena Muenzker is a Marie Curie PhD Fellow in the FragNet program under the supervision of Dr. Wolfgang Jahnke and Dr. Andreas Marzinzik in the Chemical Biology and Therapeutics Department at Novartis Basel, Switzerland, and Prof. Gerhard Klebe at the Philipps-Universität Marburg, Germany. She graduated with a Master's Degree in Biological Chemistry from the University of Vienna in 2015. During her studies, she did a 6-month internship on the synthesis of oligosaccharides at Synphabase, Switzerland, and carried out her Master's Project in Prof. Paul Robert Hansen's lab at the University of Copenhagen focusing on lipidated cyclic and bicyclic antimicrobial peptide synthesis. After her studies, she took the opportunity to join Prof. Nathanael Gray's lab at the Dana Farber Cancer Institute and learned new methods related to protein kinase inhibitors. She will expand her experience in her PhD project, which comprises structural biophysics and FBDD to identify novel inhibitors of Trypanosoma brucei FPPS.

image PDF   |   image HTML
 

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords