Conjugates of Chloramphenicol Amine and Berberine as Antimicrobial Agents.

In order to obtain antimicrobial compounds with improved properties, new conjugates comprising two different biologically active agents within a single chimeric molecule based on chloramphenicol (CHL) and a hydrophobic cation were synthesized and studied. Chloramphenicol amine (CAM), derived from the ribosome-targeting antibiotic CHL, and the plant isoquinoline alkaloid berberine (BER) are connected by alkyl linkers of different lengths in structures of these conjugates. Using competition binding, double reporter system, and toeprinting assays, we showed that synthesized CAM-Cn-BER compounds bound to the bacterial ribosome and inhibited protein synthesis like the parent CHL.

Peculiarities in Activation of Hydrolytic Activity of Elongation Factors.

Translational GTPases (trGTPases) belong to the family of G proteins and play key roles at all stages of protein biosynthesis on the ribosome. Unidirectional and cyclic functioning of G proteins is ensured by their ability to switch between the active and inactive states due to GTP hydrolysis accelerated by the auxiliary GTPase-activating proteins. Although trGTPases interact with the ribosomes in different conformational states, they bind to the same conserved region, which, unlike in classical GTPase-activating proteins, is represented by ribosomal RNA.