Medicinal chemistry articles within Nature Communications

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• Article | 23 October 2012

  Ca_V1.3-selective L-type calcium channel antagonists as potential new therapeutics for Parkinson's disease

  L-type calcium channels comprising the Ca_V1.3 subunit have been linked to the generation of mitochondrial oxidant stress in Parkinson’s disease. Kang et al. identify pyrimidine-2,4,6-triones as a potential molecular scaffold, which they modify to develop a potent and highly selective Ca_V1.3 antagonist.

  • Soosung Kang
  • , Garry Cooper
  •  & Richard B. Silverman

• Article | 22 November 2011

  TRPA1 mediates spinal antinociception induced by acetaminophen and the cannabinoid Δ⁹-tetrahydrocannabiorcol

  TRPA1 is a key ion channel in pain signalling. This study shows that activation of TRPA1 in the spinal cord by acetaminophen metabolites and a non-electrophilic cannabinoid produces antinociception that is lost in mice lacking TRPA1, providing an explanation for the analgesic activity of acetaminophen.

  • David A Andersson
  • , Clive Gentry
  •  & Peter M Zygmunt

• Article | 08 November 2011

  Malaria parasite tyrosyl-tRNA synthetase secretion triggers pro-inflammatory responses

  Parasites such as malaria elicit an immune response in their host, causing cytokine levels to increase. In this study, a parasite housekeeping gene, tyrosyl-tRNA synthetase, is shown to bind to host macrophages and, once inside the cells, enhance the levels of proinflammatory cytokines.

  • Tarun Kumar Bhatt
  • , Sameena Khan
  •  & Amit Sharma

• Article | 11 October 2011

  A mitochondria-targeted inhibitor of cytochrome c peroxidase mitigates radiation-induced death

  Radiomitigating compounds could be used to protect against ionizing radiation. In this study, mitochondria-targeted oleic and stearic acid derivatives are shown to inhibit pro-apoptotic oxidative events, prevent cell death, and protect mice against lethal doses of radiation.

  • Jeffrey Atkinson
  • , Alexandr A. Kapralov
  •  & Valerian E. Kagan

• Article
  12 July 2011 | Open Access

  Mechanism of 150-cavity formation in influenza neuraminidase

  Group-1 influenza A neuramidase proteins have a 150-cavity that can be targeted by drugs, but the 2009 H1N1 virus neuramidase is not thought to have a 150-cavity. Here, biophysical simulations show that the 2009 H1N1 neuramidase exists in solution with an open 150-cavity, which is stabilized by a salt bridge.

  • Rommie E. Amaro
  • , Robert V. Swift
  •  & Robin M. Bush

• Article | 05 October 2010

  Development of a novel selective inhibitor of the Down syndrome-related kinase Dyrk1A

  The kinase Dyrk1A is essential for brain function and development, and its excessive activity has been implicated in Down syndrome. In this study, a selective inhibitor of Dyrk1A is developed, which may help to elucidate the molecular mechanisms of normal and diseased brain.

  • Yasushi Ogawa
  • , Yosuke Nonaka
  •  & Masatoshi Hagiwara