35530-10-0Relevant articles and documents
Interaction of chloramphenicol tripeptide analogs with ribosomes
Tereshchenkov,Shishkina,Tashlitsky,Korshunova,Bogdanov,Sumbatyan
, p. 392 - 400 (2016)
Chloramphenicol amine peptide derivatives containing tripeptide fragments of regulatory “stop peptides”–MRL, IRA, IWP–were synthesized. The ability of the compounds to form ribosomal complexes was studied by displacement of the fluorescent erythromycin an
Binding and Action of Amino Acid Analogs of Chloramphenicol upon the Bacterial Ribosome
Tereshchenkov, Andrey G.,Dobosz-Bartoszek, Malgorzata,Osterman, Ilya A.,Marks, James,Sergeeva, Vasilina A.,Kasatsky, Pavel,Komarova, Ekaterina S.,Stavrianidi, Andrey N.,Rodin, Igor A.,Konevega, Andrey L.,Sergiev, Petr V.,Sumbatyan, Natalia V.,Mankin, Alexander S.,Bogdanov, Alexey A.,Polikanov, Yury S.
, p. 842 - 852 (2018/02/26)
Antibiotic chloramphenicol (CHL) binds with a moderate affinity at the peptidyl transferase center of the bacterial ribosome and inhibits peptide bond formation. As an approach for modifying and potentially improving properties of this inhibitor, we explored ribosome binding and inhibitory activity of a number of amino acid analogs of CHL. The L-histidyl analog binds to the ribosome with the affinity exceeding that of CHL by 10 fold. Several of the newly synthesized analogs were able to inhibit protein synthesis and exhibited the mode of action that was distinct from the action of CHL. However, the inhibitory properties of the semi-synthetic CHL analogs did not correlate with their affinity and in general, the amino acid analogs of CHL were less active inhibitors of translation in comparison with the original antibiotic. The X-ray crystal structures of the Thermus thermophilus 70S ribosome in complex with three semi-synthetic analogs showed that CHL derivatives bind at the peptidyl transferase center, where the aminoacyl moiety of the tested compounds established idiosyncratic interactions with rRNA. Although still fairly inefficient inhibitors of translation, the synthesized compounds represent promising chemical scaffolds that target the peptidyl transferase center of the ribosome and potentially are suitable for further exploration.
STEREOSELECTIVE SYNTHESIS OF (+/-)-threo-2-AMINO-1-(4-NITROPHENYL)-1,3-PROPANEDIOL
Cervinka, Otakar,Dudek, Vaclav,Fabryova, Anna,Kolar, Jiri,Lukac, Juraj,et al.
, p. 2748 - 2752 (2007/10/02)
Addition of hypobromic acid to styrene afforded styrene bromohydrin (I) which was dehydrated to ω-bromostyrene (II).Prince reaction of II with aqueous formaldehyde gave 5-bromo-4-phenyl-1,3-dioxane (III).The bromine atom in III was replaced with amino group by treatment with methanolic ammonia at 150 deg C and 6 - 8 MPa and the obtained threo-5-amino-4-phenyl-1,3-dioxane (IVa) was hydrolyzed to give (+/-)-threo-2-amino-1-phenyl-1,3-propanediol (V).Suitably chosen method of nitration converted the free base IVa or its N-acetyl derivative IVb into 5-amino-4-(4-nitrophe nyl)-1,3-dioxane (VIa) or its N-acetyl derivative VIb which without isolation were hydrolyzed to threo-2-amino-1-(4-nitrophenyl)-1,3-propanediol (VII), isolated as hydrochloride.The liberated base was resolved into enantiomers and dichloroacetylated in the known manner to give D-(-)-threo-2-dichloroacetylamino-1-(4-nitrophenyl)-1,3-propanediol (chloramphenicol).
