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Phototriggerable peptidomimetics for the inhibition of Mycobacterium tuberculosis ribonucleotide reductase by targeting protein–protein binding

2014; Royal Society of Chemistry; Volume: 13; Issue: 9 Linguagem: Inglês

10.1039/c4ob01926a

1477-0539

Christoffer Karlsson, Magnus Blom, Miranda Johansson, Anna Jansson, Enzo Scifo, Anders Karlén, Thavendran Govender, Adolf Gogoll,

Click Chemistry and Applications

Incorporation of an artificial amino acid 2 with a stilbene chromophore into peptidomimetics with three to nine amino acids yields phototriggerable candidates for inhibition of the binding between the R1 and R2 subunits of the M. tuberculosis ribonucleotide reductase (RNR). Interstrand hydrogen bond probability was used as a guideline for predicting conformational preferences of the photoisomers. Binding of these inhibitors has been rationalized by docking studies with the R1 unit. Significant differences in binding of the photoisomers were observed. For the shorter peptidomimetics, stronger binding of the Z isomer might indicate hydrophobic interactions between the stilbene chromophore and the binding site.