Host Cell Interactions Are a Significant Barrier to the Clinical Utility of Peptide Antibiotics

November 7th, 2016 by Charles G. Starr, Jing He and William C. Wimley

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ACS Chemical Biology
DOI: 10.1021/acschembio.6b00843

Genetic engineering: Chemical control for CRISPR editing

November 7th, 2016 by Isaac B Hilton

Nature Chemical Biology 13, 2 (2017). doi:10.1038/nchembio.2243

Authors: Isaac B Hilton & Charles A Gersbach

New approaches allow tight control over Cas9 activity using chemical induction. These studies expand the ability to rapidly induce and suppress Cas9-mediated nuclease activity and conditionally modulate the multiplex regulation of endogenous gene expression.

Identification of G-quadruplexes in long functional RNAs using 7-deazaguanine RNA

November 7th, 2016 by Carika Weldon

Nature Chemical Biology 13, 18 (2017). doi:10.1038/nchembio.2228

Authors: Carika Weldon, Isabelle Behm-Ansmant, Laurence H Hurley, Glenn A Burley, Christiane Branlant, Ian C Eperon & Cyril Dominguez

RNA G-quadruplex (G4) structures are thought to affect biological processes, including translation and pre-mRNA splicing, but it is not possible at present to demonstrate that they form naturally at specific sequences in long functional RNA molecules. We developed a new strategy, footprinting of long 7-deazaguanine-substituted RNAs (FOLDeR), that allows the formation of G4s to be confirmed in long RNAs and under functional conditions.

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DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis

November 7th, 2016 by Marian C Okondo

Nature Chemical Biology 13, 46 (2017). doi:10.1038/nchembio.2229

Authors: Marian C Okondo, Darren C Johnson, Ramya Sridharan, Eun Bin Go, Ashley J Chui, Mitchell S Wang, Sarah E Poplawski, Wengen Wu, Yuxin Liu, Jack H Lai, David G Sanford, Michael O Arciprete, Todd R Golub, William W Bachovchin & Daniel A Bachovchin

  • Posted in Nat Chem Biol, Publications
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Inhibition of RAS function through targeting an allosteric regulatory site

November 7th, 2016 by Russell Spencer-Smith

Nature Chemical Biology 13, 62 (2017). doi:10.1038/nchembio.2231

Authors: Russell Spencer-Smith, Akiko Koide, Yong Zhou, Raphael R Eguchi, Fern Sha, Priyanka Gajwani, Dianicha Santana, Ankit Gupta, Miranda Jacobs, Erika Herrero-Garcia, Jacqueline Cobbert, Hugo Lavoie, Matthew Smith, Thanashan Rajakulendran, Evan Dowdell, Mustafa Nazir Okur, Irina Dementieva, Frank Sicheri, Marc Therrien, John F Hancock, Mitsuhiko Ikura, Shohei Koide & John P O'Bryan

  • Posted in Nat Chem Biol, Publications
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Non-classical transpeptidases yield insight into new antibacterials

November 7th, 2016 by Pankaj Kumar

Nature Chemical Biology 13, 54 (2017). doi:10.1038/nchembio.2237

Authors: Pankaj Kumar, Amit Kaushik, Evan P Lloyd, Shao-Gang Li, Rohini Mattoo, Nicole C Ammerman, Drew T Bell, Alexander L Perryman, Trevor A Zandi, Sean Ekins, Stephan L Ginell, Craig A Townsend, Joel S Freundlich & Gyanu Lamichhane

A multi-step peptidolytic cascade for amino acid recovery in chloroplasts

October 31st, 2016 by Pedro F Teixeira

Nature Chemical Biology 13, 15 (2017). doi:10.1038/nchembio.2227

Authors: Pedro F Teixeira, Beata Kmiec, Rui M M Branca, Monika W Murcha, Anna Byzia, Aneta Ivanova, James Whelan, Marcin Drag, Janne Lehtiö & Elzbieta Glaser

Plastids (including chloroplasts) are subcellular sites for a plethora of proteolytic reactions, required in functions ranging from protein biogenesis to quality control. Here we show that peptides generated from pre-protein maturation within chloroplasts of Arabidopsis thaliana are degraded to amino acids by a multi-step peptidolytic cascade consisting of oligopeptidases and aminopeptidases, effectively allowing the recovery of single amino acids within these organelles.

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Genome-wide genetic screening with chemically mutagenized haploid embryonic stem cells

October 31st, 2016 by Josep V Forment

Nature Chemical Biology 13, 12 (2017). doi:10.1038/nchembio.2226

Authors: Josep V Forment, Mareike Herzog, Julia Coates, Tomasz Konopka, Bianca V Gapp, Sebastian M Nijman, David J Adams, Thomas M Keane & Stephen P Jackson

In model organisms, classical genetic screening via random mutagenesis provides key insights into the molecular bases of genetic interactions, helping to define synthetic lethality, synthetic viability and drug-resistance mechanisms. The limited genetic tractability of diploid mammalian cells, however, precludes this approach. Here, we demonstrate the feasibility of classical genetic screening in mammalian systems by using haploid cells, chemical mutagenesis and next-generation sequencing, providing a new tool to explore mammalian genetic interactions.

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Multidimensional chemical control of CRISPR–Cas9

October 31st, 2016 by Basudeb Maji

Nature Chemical Biology 13, 9 (2017). doi:10.1038/nchembio.2224

Authors: Basudeb Maji, Christopher L Moore, Bernd Zetsche, Sara E Volz, Feng Zhang, Matthew D Shoulders & Amit Choudhary

Cas9-based technologies have transformed genome engineering and the interrogation of genomic functions, but methods to control such technologies across numerous dimensions—including dose, time, specificity, and mutually exclusive modulation of multiple genes—are still lacking. We conferred such multidimensional controls to diverse Cas9 systems by leveraging small-molecule-regulated protein degron domains. Application of our strategy to both Cas9-mediated genome editing and transcriptional activities opens new avenues for systematic genome interrogation.

Dereplication of peptidic natural products through database search of mass spectra

October 31st, 2016 by Hosein Mohimani

Nature Chemical Biology 13, 30 (2017). doi:10.1038/nchembio.2219

Authors: Hosein Mohimani, Alexey Gurevich, Alla Mikheenko, Neha Garg, Louis-Felix Nothias, Akihiro Ninomiya, Kentaro Takada, Pieter C Dorrestein & Pavel A Pevzner

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