In this issue - pv

doi:10.1038/nchembio0709-v

Full Text - In this issue | PDF (293 KB) - In this issue

Perfecting probes - p435

doi:10.1038/nchembio0709-435

Identifying and increasing access to the highest quality chemical probes will ensure their prominent position in the biological and drug discovery toolboxes.

Full Text - Perfecting probes | PDF (112 KB) - Perfecting probes

Open access chemical and clinical probes to support drug discovery - pp436 - 440

Aled M Edwards, Chas Bountra, David J Kerr & Timothy M Willson

doi:10.1038/nchembio0709-436

Abstract - Open access chemical and clinical probes to support drug discovery | Full Text - Open access chemical and clinical probes to support drug discovery | PDF (142 KB) - Open access chemical and clinical probes to support drug discovery | Supplementary information

A crowdsourcing evaluation of the NIH chemical probes - pp441 - 447

Tudor I Oprea, Cristian G Bologa, Scott Boyer, Ramona F Curpan, Robert C Glen, Andrew L Hopkins, Christopher A Lipinski, Garland R Marshall, Yvonne C Martin, Liliana Ostopovici-Halip, Gilbert Rishton, Oleg Ursu, Roy J Vaz, Chris Waller, Herbert Waldmann & Larry A Sklar

doi:10.1038/nchembio0709-441

Abstract - A crowdsourcing evaluation of the NIH chemical probes | Full Text - A crowdsourcing evaluation of the NIH chemical probes | PDF (554 KB) - A crowdsourcing evaluation of the NIH chemical probes | Supplementary information

Inhibitors paradoxically prime kinases - pp448 - 449

Stephen V Frye & Gary L Johnson

doi:10.1038/nchembio.f.11

Small-molecule inhibitors can induce phosphorylation priming of AGC kinases. Priming by ATP binding pocket conformation, rather than intrinsic kinase activity, has significant implications for drug discovery and therapeutic efficacy.

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See also: Article by Okuzumi et al.

Hidden biosynthetic treasures brought to light - pp450 - 452

Christian Hertweck

doi:10.1038/nchembio0709-450

Microorganisms are a major source of new therapeutics. However, the discovery and sustainable production of these compounds are often hampered owing to limited access to biosynthetic genes or products. Recent studies provide new approaches for targeting biosynthesis genes in the metagenome of complex microbial assemblages and for inducing the expression of otherwise silent biosynthesis genes.

Full Text - Hidden biosynthetic treasures brought to light | PDF (1,272 KB) - Hidden biosynthetic treasures brought to light

See also: Brief Communication by Bok et al. | Article by Fisch et al.

Encoding chemistry - pp452 - 453

Dario Neri & André W Brändli

doi:10.1038/nchembio0709-452

A new methodology combining small molecules and phage-displayed peptides enables the isolation of chemically modified bicyclic peptides capable of high-affinity recognition of target proteins.

Full Text - Encoding chemistry | PDF (1,718 KB) - Encoding chemistry

See also: Article by Heinis et al.

Acetoacetate decarboxylase: hydrophobics, not electrostatics - pp454 - 455

John A Gerlt

doi:10.1038/nchembio0709-454

Westheimer's classical proposal that the decreased pK_a of Lys115 in the active site of acetoacetate decarboxylase is the result of its unfavorable electrostatic juxtaposition with Lys116 has been evaluated by X-ray crystallography. The long-awaited structure reveals that Lys115 is positioned in a hydrophobic pocket that lowers its pK_a.

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Research highlights - pp456 - 457

doi:10.1038/nchembio0709-456

Full Text - Research highlights | PDF (147 KB) - Research highlights