title: Phototriggerable peptidomimetics for the inhibition of Mycobacterium tuberculosis ribonucleotide reductase by targeting protein-protein binding.
abstract: 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.
authors.affiliation: Department of Chemistry - BMC, Uppsala University, Box 576, S-751 23 Uppsala, Sweden. adolf.gogoll@kemi.uu.se.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Karlsson
authors.forename: Magnus
authors.initials: M
authors.lastname: Blom
authors.forename: Miranda
authors.initials: M
authors.lastname: Johansson
authors.forename: Anna M
authors.initials: AM
authors.lastname: Jansson
authors.forename: Enzo
authors.initials: E
authors.lastname: Scifo
authors.forename: Anders
authors.initials: A
authors.lastname: Karlén
authors.forename: Thavendran
authors.initials: T
authors.lastname: Govender
authors.forename: Adolf
authors.initials: A
authors.lastname: Gogoll
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D057786:Peptidomimetics; D055668:Photochemical Processes; D011485:Protein Binding / Q000187:drug effects; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D004791:Enzyme Inhibitors; D057786:Peptidomimetics; D013267:Stilbenes; D012264:Ribonucleotide Reductases