Modular synthesis enables molecular ju-jitsu

[...]modularity is a powerful enabler of creativity: because many variants can be rapidly assembled and tested, researchers can make almost any target that they want. [...]unlike conventional small-molecule synthesis, the price of failure is not high - it doesn't matter if any given compound la...

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Bibliographic Details
Published inNature (London) Vol. 586; no. 7827; pp. 32 - 33
Main Authors Blair, Daniel J, Burke, Martin D
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group 01.10.2020
Subjects
Amino acids
Antibiotics
Binding sites
Biological activity
Chemical synthesis
Crystal structure
Enzymes
Microscopy
Modularity
Nucleotides
Protein synthesis
Streptogramins
Tunnels
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Summary:[...]modularity is a powerful enabler of creativity: because many variants can be rapidly assembled and tested, researchers can make almost any target that they want. [...]unlike conventional small-molecule synthesis, the price of failure is not high - it doesn't matter if any given compound lacks the desired biological activity, because many others can be prepared, thereby increasing the likelihood of finding active small molecules. [...]the allyl group points towards the binding site for group B streptogramins in the exit tunnel, and seems to make favourable contacts with three nucleotides in the tunnel that are not contacted by VM2. Li et al. also obtained an X-ray crystal structure of the new compound bound to VatA, which revealed a potential clash between the allyl group and an amino-acid residue (designated Leu 110) in the enzyme.
ISSN:0028-0836
1476-4687
DOI:10.1038/d41586-020-02565-1