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Activity-Based Protein Profiling for Natural Product Target Discovery

  • Joanna Krysiak
  • Rolf Breinbauer
Chapter
Part of the Topics in Current Chemistry book series (TOPCURRCHEM, volume 324)

Abstract

Natural products represent an important treasure box of biologically active molecules, from which many drug candidates have been sourced. The identification of the target proteins addressed by these natural products is a foremost goal for which new techniques are required. Activity-based protein profiling (ABPP), exploiting protein-reactive functional groups present in many natural products, offers unseen opportunities in this respect. This review article describes the current status of this field. Many examples are given for the annotation of biological target proteins of natural products containing epoxides, lactones, lactams, Michael acceptors, and other electrophilic groups. In addition, the development of probe molecules identified from biomimetic natural product libraries is discussed.

Keywords

Activity-based protein profiling Chemical biology Molecular probes Natural products Target profiling 

Abbreviations

ABPP

Activity-based protein profiling

ADPKD

Autosomal dominant polycystic kidney disease

AGT

Alkylguanine DNA alkyltransferase

Asn

Asparagine

ATP

Adenosine triphosphate

BG

Benzylguanine

BIOS

Biology-oriented synthesis

BODIPY

Boron-dipyrromethane fluorescent dye

Cys

Cysteine

DNA

Deoxyribonucleic acid

DOS

Diversity-oriented synthesis

FAS

Fatty acid synthase

FDA

Food and Drug Administration

GT

Glutamyl transpeptidase

HSP

Heat shock protein

HUVEC

Human umbilical venous endothelial cells

IC50

Half maximal inhibitory concentration

Lys

Lysine

MALDI

Maxtrix-assisted laser desorption ionization

MIC

Minimal inhibitory concentration

MRSA

Methicillin-resistant Staphylococcus aureus

MS

Mass spectrometry

NES

Nuclear export sequence

PAGE

Polyacrylamide gel electrophoresis

PBP

Penicillin binding protein

PIKK

Phosphoinositoide 3-kinase related kinase

PP

Protein phosphatase

RNA

Ribonucleic acid

S

Svedberg unit

SDS

Sodium dodecylsulfate

Ser

Serine

TAMRA

Tetramethyl-5(6)-carboxyrhodamine dye

THL

Tetrahydrolipstatin

Thr

Threonine

UDP

Uridine diphosphate

UMP

Uridine monophosphate

Notes

Acknowledgements

R.B. thanks the Austrian Science Fund (FWF) for a PhD scholarship for J.K. (Doktoratskolleg “Molecular Enzymology” W901-B05), and the PLACEBO (Platform for Chemical Biology)-project as part of the Austrian Genome Project GEN-AU funded by the Forschungsförderungsgesellschaft und Bundesministerium für Wissenschaft und Forschung for research funding.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Institute of Organic ChemistryGraz University of TechnologyGrazAustria

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