Target validation articles within Nature Chemistry

Featured

• Article | 19 September 2022

  Synthesis and single-molecule imaging reveal stereospecific enhancement of binding kinetics by the antitumour eEF1A antagonist SR-A3

  The total synthesis and complete stereochemical assignment of the cyclic peptide natural product SR-A3—which has potential as a cancer therapeutic—has now been reported. Single-molecule biophysical and cellular experiments reveal a crucial, stereospecific role for a side-chain hydroxyl in SR-A3, which confers enhanced target residence time and efficacy in a mouse tumour model.

  • Hao-Yuan Wang
  • , Haojun Yang
  •  & Jack Taunton

• Article | 16 December 2019

  Repurposing human kinase inhibitors to create an antibiotic active against drug-resistant Staphylococcus aureus, persisters and biofilms

  Screening commercial kinase inhibitors for antibacterial activity identified the anticancer drug sorafenib as a major hit. Subsequent structure–activity optimization created a new antibacterial analogue with high potency against methicillin-resistant Staphylococcus aureus, including challenging persisters and biofilms, as well as demonstrating efficacy in an in vivo mouse model. The mode of action involves stimulation of protein secretion and inhibition of menaquinone biosynthesis.

  • Philipp Le
  • , Elena Kunold
  •  & Stephan A. Sieber

• Article | 14 May 2018

  Fragment-derived inhibitors of human N-myristoyltransferase block capsid assembly and replication of the common cold virus

  An effective antiviral against the common cold could prevent exacerbations in asthma and chronic obstructive pulmonary disease, but the diversity and adaptability of the virus makes it a highly challenging target. Now, picomolar inhibitors of a human lipid transferase have been developed. Targeting this human lipid transferase could provide an effective and broad-spectrum approach to block viral replication in the host.

  • Aurélie Mousnier
  • , Andrew S. Bell
  •  & Edward W. Tate

• Article | 09 November 2015

  Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation

  Copper is a transition metal ion essential for the regulation of cellular oxidative stress and ATP production. Now, the inhibition of copper-trafficking proteins by a small molecule has been shown to significantly reduce proliferation of cancer cells. The results indicate that copper-trafficking proteins could represent new anti-tumour therapeutic targets.

  • Jing Wang
  • , Cheng Luo
  •  & Chuan He

• News & Views | 23 January 2014

  Knockout for malaria

  Discovering and validating new targets is urgently required to tackle the rise in resistance to antimalarial drugs. Now, inhibition of the enzyme N-myristoyltransferase has been shown to prevent the formation of a critical subcellular organelle in the parasite that causes malaria, leading to death of the parasite.

  • Joanna Krysiak
  •  & Stephan A. Sieber

• Article | 22 December 2013

  Validation of N-myristoyltransferase as an antimalarial drug target using an integrated chemical biology approach

  Chemical validation of new drug targets is urgently required to help develop new antimalarial therapies. Here, chemical proteomic tools and selective enzyme inhibitors are combined to study protein lipidation in human malaria parasites, leading to in vitro and in vivo validation of the enzyme N-myristoyltransferase as a drug target.

  • Megan H. Wright
  • , Barbara Clough
  •  & Edward W. Tate