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Chemical Genetics
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Chemical Genetics

A special issue of Molecules (ISSN 1420-3049).

Deadline for manuscript submissions: closed (31 August 2012) | Viewed by 48184

Special Issue Editor

Dr. Richard YT Kao

E-Mail Website
Guest Editor
Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
Interests: chemical biology; chemical genetics; druggable targets; small molecule inhibitors; infectious diseases; antimicrobials; angiogenesis

Special Issue Information

Dear Colleagues,

Since its name being coined more than a decade ago, chemical genetics has been increasingly recognized as an effective technique in dissecting complicated biological processes difficult to be studied by conventional classical genetics approaches. The applications of chemical genetics are phenomenon and many disciplines such as cellular biology, cancer research, developmental biology, plant science, microbiology, drug discovery, etc., have been benefited greatly from this powerful methodology. New chemical compounds, probes, and novel screening procedures and informatics have been invented and applied to drive the rapid evolution of this powerful technique. This special issue on Chemical Genetics offers possibilities for colleagues to illustrate latest applications of chemical genetics in various disciplines and new technologies employed to enhance the capabilities of this evolving methodology.

Dr. Richard YT Kao
Guest Editor

Keywords

  • chemical genetics
  • chemical biology
  • small molecule compounds
  • inhibitors
  • activators
  • chemical probes
  • informatics
  • high-throughput Screening
  • drug discovery

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Published Papers (5 papers)

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Research

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497 KiB  
Article
Discovery and Validation of SIRT2 Inhibitors Based on Tenovin-6: Use of a 1H-NMR Method to Assess Deacetylase Activity
by Lisa Pirrie, Anna R. McCarthy, Louise L. Major, Vaida Morkūnaitė, Asta Zubrienė, Daumantas Matulis, Sonia Lain, Tomas Lebl and Nicholas J. Westwood
Molecules 2012, 17(10), 12206-12224; https://doi.org/10.3390/molecules171012206 - 18 Oct 2012
Cited by 10 | Viewed by 9417
Abstract
The search for potent and selective sirtuin inhibitors continues as chemical tools of this type are of use in helping to assign the function of this interesting class of deacetylases. Here we describe SAR studies starting from the unselective sirtuin inhibitor tenovin-6. These [...] Read more.
The search for potent and selective sirtuin inhibitors continues as chemical tools of this type are of use in helping to assign the function of this interesting class of deacetylases. Here we describe SAR studies starting from the unselective sirtuin inhibitor tenovin-6. These studies identify a sub-micromolar inhibitor that has increased selectivity for SIRT2 over SIRT1 compared to tenovin-6. In addition, a 1H-NMR-based method is developed and used to validate further this class of sirtuin inhibitors. A thermal shift analysis of SIRT2 in the presence of tenovin-6, -43, a control tenovin and the known SIRT2 inhibitor AGK2 is also presented. Full article
(This article belongs to the Special Issue Chemical Genetics)
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Review

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401 KiB  
Review
Forward Chemical Genetics in Yeast for Discovery of Chemical Probes Targeting Metabolism
by Robert St.Onge, Ulrich Schlecht, Curt Scharfe and Marie Evangelista
Molecules 2012, 17(11), 13098-13115; https://doi.org/10.3390/molecules171113098 - 5 Nov 2012
Cited by 15 | Viewed by 14031
Abstract
The many virtues that made the yeast Saccharomyces cerevisiae a dominant model organism for genetics and molecular biology, are now establishing its role in chemical genetics. Its experimental tractability (i.e., rapid doubling time, simple culture conditions) and the availability of powerful [...] Read more.
The many virtues that made the yeast Saccharomyces cerevisiae a dominant model organism for genetics and molecular biology, are now establishing its role in chemical genetics. Its experimental tractability (i.e., rapid doubling time, simple culture conditions) and the availability of powerful tools for drug-target identification, make yeast an ideal organism for high-throughput phenotypic screening. It may be especially applicable for the discovery of chemical probes targeting highly conserved cellular processes, such as metabolism and bioenergetics, because these probes would likely inhibit the same processes in higher eukaryotes (including man). Importantly, changes in normal cellular metabolism are associated with a variety of diseased states (including neurological disorders and cancer), and exploiting these changes for therapeutic purposes has accordingly gained considerable attention. Here, we review progress and challenges associated with forward chemical genetic screening in yeast. We also discuss evidence supporting these screens as a useful strategy for discovery of new chemical probes and new druggable targets related to cellular metabolism. Full article
(This article belongs to the Special Issue Chemical Genetics)
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443 KiB  
Review
The Final Link: Tapping the Power of Chemical Genetics to Connect the Molecular and Biologic Functions of Mitotic Protein Kinases
by Robert F. Lera and Mark E. Burkard
Molecules 2012, 17(10), 12172-12186; https://doi.org/10.3390/molecules171012172 - 17 Oct 2012
Cited by 3 | Viewed by 8815
Abstract
During mitosis, protein kinases coordinate cellular reorganization and chromosome segregation to ensure accurate distribution of genetic information into daughter cells. Multiple protein kinases contribute to mitotic regulation, modulating molecular signaling more rapidly than possible with gene expression. However, a comprehensive understanding of how [...] Read more.
During mitosis, protein kinases coordinate cellular reorganization and chromosome segregation to ensure accurate distribution of genetic information into daughter cells. Multiple protein kinases contribute to mitotic regulation, modulating molecular signaling more rapidly than possible with gene expression. However, a comprehensive understanding of how kinases regulate mitotic progression remains elusive. The challenge arises from multiple functions and substrates, a large number of “bystander” phosphorylation events, and the brief window in which all mitotic events transpire. Analog-sensitive alleles of protein kinases are powerful chemical genetic tools for rapid and specific interrogation of kinase function. Moreover, combining these tools with advanced proteomics and substrate labeling has identified phosphorylation sites on numerous protein targets. Here, we review the chemical genetic tools available to study kinase function and identify substrates. We describe how chemical genetics can also be used to link kinase function with cognate phosphorylation events to provide mechanistic detail. This can be accomplished by dissecting subsets of kinase functions and chemical genetic complementation. We believe a complete “chemical genetic toolbox” will ultimately allow a comprehensive understanding of how protein kinases regulate mitosis. Full article
(This article belongs to the Special Issue Chemical Genetics)
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576 KiB  
Review
Chemical Genetics — A Versatile Method to Combine Science and Higher Level Teaching in Molecular Genetics
by Björn Sandrock
Molecules 2012, 17(10), 11920-11930; https://doi.org/10.3390/molecules171011920 - 9 Oct 2012
Cited by 3 | Viewed by 6990
Abstract
Phosphorylation is a key event in many cellular processes like cell cycle, transformation of environmental signals to transcriptional activation or polar growth. The chemical genetics approach can be used to analyse the effect of highly specific inhibition in vivo and is a promising [...] Read more.
Phosphorylation is a key event in many cellular processes like cell cycle, transformation of environmental signals to transcriptional activation or polar growth. The chemical genetics approach can be used to analyse the effect of highly specific inhibition in vivo and is a promising method to screen for kinase targets. We have used this approach to study the role of the germinal centre kinase Don3 during the cell division in the phytopathogenic fungus Ustilago maydis. Due to the easy determination of the don3 phenotype we have chosen this approach for a genetic course for M.Sc. students and for IMPRS (International Max-Planck research school) students. According to the principle of “problem-based learning” the aim of this two-week course is to transfer knowledge about the broad spectrum of kinases to the students and that the students acquire the ability to design their own analog-sensitive kinase of interest. In addition to these training goals, we benefit from these annual courses the synthesis of basic constructs for genetic modification of several kinases in our model system U. maydis. Full article
(This article belongs to the Special Issue Chemical Genetics)
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321 KiB  
Review
Chemical Genetics: Budding Yeast as a Platform for Drug Discovery and Mapping of Genetic Pathways
by Jorrit M. Enserink
Molecules 2012, 17(8), 9258-9273; https://doi.org/10.3390/molecules17089258 - 2 Aug 2012
Cited by 14 | Viewed by 7772
Abstract
The budding yeast Saccharomyces cerevisiae is a widely used model organism, and yeast genetic methods are powerful tools for discovery of novel functions of genes. Recent advancements in chemical-genetics and chemical-genomics have opened new avenues for development of clinically relevant drug treatments. Systematic [...] Read more.
The budding yeast Saccharomyces cerevisiae is a widely used model organism, and yeast genetic methods are powerful tools for discovery of novel functions of genes. Recent advancements in chemical-genetics and chemical-genomics have opened new avenues for development of clinically relevant drug treatments. Systematic mapping of genetic networks by high-throughput chemical-genetic screens have given extensive insight in connections between genetic pathways. Here, I review some of the recent developments in chemical-genetic techniques in budding yeast. Full article
(This article belongs to the Special Issue Chemical Genetics)
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