Chemical proteome mining for functional annotation of disease relevant proteins

Projektinformationen

CHEMMINE

ID Finanzhilfevereinbarung: 725085

DOI 10.3030/725085

Abgeschlossenes Projekt

EK-Unterschriftsdatum 6 Februar 2017

Startdatum 1 März 2017

Enddatum 31 August 2022

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten € 1 936 250,00

EU-Beitrag € 1 936 250,00

Koordiniert durch

TECHNISCHE UNIVERSITAET MUENCHEN
Germany

Ziel

Genome sequencing projects have provided unique insights into the cellular inventory of genes and their corresponding protein products. Despite this success, a large fraction of cellular proteins remains functionally uncharacterized. Their annotation represents a major challenge for contemporary research, reaching beyond the power of bioinformatic sequence similarity searches. Thus multidisciplinary strategies consolidating chemical and biological methods are required to close this gap. We here approach the challenge by two chemical proteomic platforms that focus on disease relevant sub-fractions of the uncharacterized proteome. The first platform utilizes functionalized cofactors that exploit cognate cellular uptake systems and report specific binding of large enzyme families. The molecules will be applied to mine cellular proteomes for unknown family members with crucial roles in diseases and assign their function. The second platform exploits phosphoaspartate as an important disease-related post-translational modification. Due to low stability, this transient modification currently escapes detection by established proteomic procedures. Moreover, little is known about the enzymes that catalyze aspartate phosphorylation. We here use specific nucleophilic traps that convert phosphoaspartate into stable modifications suitable for analytic detection. In addition, the complement of currently unknown phosphodonor proteins will be identified with customized tools. With these platforms we aim to functionally annotate sub-fractions of the uncharacterized proteome and utilize our tools for the identification of new drug targets by comparative analysis of healthy and diseased cells. Finally, we apply the camouflaged molecular design strategy in the synthesis of compound libraries to screen for candidate inhibitors against selected, disease-modulating targets. The previous record of my group in chemical proteomics provides a strong basis to achieve these challenging goals.

Wissenschaftliches Gebiet

• natural sciences › biological sciences › biochemistry › biomolecules › proteins › proteomics
• natural sciences › biological sciences › genetics › genomes
• natural sciences › biological sciences › biochemistry › biomolecules › proteins › enzymes

Schlüsselbegriffe

• Chemical proteomics
• enzyme function
• cofactors
• probes
• synthesis
• post-translational modification
• phosphorylation
• mass-spectrometry
• biological activity

Programm/Programme

• H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme

Thema/Themen

• ERC-2016-COG - ERC Consolidator Grant

Aufforderung zur Vorschlagseinreichung

ERC-2016-COG

Finanzierungsplan

ERC-COG - Consolidator Grant

Gastgebende Einrichtung

TECHNISCHE UNIVERSITAET MUENCHEN

• Netto-EU-Beitrag: € 1 936 250,00
• Adresse: Arcisstrasse 21 ; 80333 Muenchen ; Deutschland
• Region: Bayern › Oberbayern › München, Kreisfreie Stadt
• Aktivitätstyp: Higher or Secondary Education Establishments
• Gesamtkosten: € 1 936 250,00

Begünstigte (1)

TECHNISCHE UNIVERSITAET MUENCHEN

Deutschland

• Netto-EU-Beitrag: € 1 936 250,00
• Adresse: Arcisstrasse 21 ; 80333 Muenchen
• Region: Bayern › Oberbayern › München, Kreisfreie Stadt
• Aktivitätstyp: Higher or Secondary Education Establishments
• Gesamtkosten: € 1 936 250,00