AOHUPO Proteome initiatives

Chemical Proteomics Initiative

Project leader: Ho Jeong KWON
Yonsei University, Korea

Objectives

Chemical proteomics is an integrated research engine that bridges over a hurdle to identify target proteins of biologically active small molecules with unknown mode of action for functional studies of proteome and drug discovery. To this end, it covers natural/synthetic chemical library construction, phenotypic screen, small molecule hits, target identification and validation, mode of action, further drug discovery against the identified target, and data base (DB) construction. The objectives of Chemical Proteomics Initiative of AOHUPO (CPI-AOHUPO) focus on systematic analysis of target protein identification of bioactive small molecules using mass spectrometry based proteome analysis and the exchange of new data and innovative technologies for better understanding of proteome and drug discovery.

Project plan

CPI-AOHUPO will initially work for 5 years as the first phase with 3+2 years at multi-laboratories of AOHUPO as follows.

The first 3 years will focus on chemical library construction, a standard cell, tissue, and phage-displayed human cDNA expressed proteome preparation, a standardized methodology development of target identification with label or label-free small molecules, and target validation and functional study of newly identified target proteins.

The following 2 years will focus on innovative technology development for proteomics based target identification of small molecules, drug discovery against the identified target, and DB construction.

After the first phase, CPI-AOHUPO may continue to another 5 years with similar scopes of the first phase and expand its activities in collaboration with other AOHUPO initiatives.

Milestones

Construction and sharing of authentic small molecule library including target known commercial library (ie., Sigma LOPAC library) and target unknown small molecules from multi-laboratories of AOHUPO.

Proteomics based technology development of target identification of label or label-free small molecules.

Target validation and functional study of newly identified target proteins.

rug discovery against the identified target and DB construction.

A coherent link with the Membrane Proteome Project

Sharing small molecule library and membrane proteome fractions to discover new small molecules or membrane proteins.

Functional studies of membrane proteome with small molecules, vice versa.

Sharing data base and informatics tools.

Joint international grant applications and organization of international meetings.

Publications resulting from the Chemical Proteomics Initiative

Ho Jeong Kwon and Peter Karuso
Chemical proteomics, an integrated research engine for exploring drug-target-phenotype interactions
Proteome Science. 2018;16(1)
doi: doi.org/10.1186/s12953-017-0129-x

Margaret L. Wong, Jason Murphy, Edmund Harrington, Carrie M. Gower, Rishi K. Jain, Markus Schirle and Jason R. Thomas
Examining the influence of specificity ligands and ATP-competitive ligands on the overall effectiveness of bivalent kinase inhibitors
Proteome Science. 2016;15:17
doi: doi.org/10.1186/s12953-017-0125-1

Michael P Gotsbacher, Sungmin Cho, Ho Jeong Kwon and Peter Karuso
Daptomycin, a last-resort antibiotic, binds ribosomal protein S19 in humans
Proteome Science. 2017;15:16
doi: 10.1186/s12953-017-0124-2

Kyungtae Kang, Jongmin Park and Eunha Kim
Tetrazine ligation for chemical proteomics
Proteome Science. 2017;15:15
doi: 10.1186/s12953-017-0121-5

Dhiraj P. Murale, Seong Cheol Hong, Md. Mamunul Haque and Jun-Seok Lee
Photo-affinity labeling (PAL) in chemical proteomics: a handy tool to investigate protein-protein interactions (PPIs)
Proteome Science. 2017;15:14
doi: 10.1186/s12953-017-0123-3

André Mateus, Tomi A. Määttä and Mikhail M. Savitski
Thermal proteome profiling: unbiased assessment of protein state through heat-induced stability changes
Proteome Science. 2016;15:13
doi: 10.1186/s12953-017-0122-4

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Publications considered for listing include congress-affiliated research, outputs from AOHUPO-coordinated initiatives, and significant contributions to proteomics science from AOHUPO member countries.

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