Premium
Sparsomycin–Linezolid Conjugates Can Promote Ribosomal Translocation
Author(s) -
Li Shibo,
Cheng Xiaofeng,
Zhou Yonghang,
Xi Zhen
Publication year - 2011
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201100508
Subject(s) - chromosomal translocation , ribosome , 23s ribosomal rna , peptidyl transferase , ribosomal rna , chemistry , moiety , biology , stereochemistry , biochemistry , rna , gene
Sparsomycin is an antibiotic that targets the peptidyl transferase center of the ribosome and has the ability to promote ribosomal translocation in the absence of EF‐G and GTP. Here we show that changes in the configurations at the two chiral centers of sparsomycin, especially at the chiral carbon, can greatly affect its capability to promote ribosomal translocation. More importantly, the incorporation of the pseudo‐uracil moiety of sparsomycin into linezolid through a covalent linkage conferred on linezolid derivatives the ability to promote translocation, thus indicating the importance of interactions between this pseudo‐uracil moiety, rRNA, and tRNA for promoting translocation. In addition, these translocation promoters can also effectively inhibit spontaneous reverse translocation; this suggests that they might promote forward translocation by trapping the ribosome in the post‐translocation state and shifting the equilibrium between the pre‐ and post‐translocation ribosome in the forward direction.