Alkaloid homoharringtonine inhibits polypeptide chain elongation on human ribosomes on the step of peptide bond formation

The aim of the present study was to investigate homoharringtonine alkaloid effect on: (i) the nonenzymatic and eEF-1-dependent Phe-tRNAphe binding to poly(U)-programmed human placenta 80 S ribosomes; (ii) diphenylalanine synthesis accompanying nonenzymatic Phe-tRNAphe binding; and (iii) acetylphenylalanyl-puromycin formation. Neither nonenzymatic nor eEF-1-dependent Phe-tRNAphe binding were noticeably affected by the alkaloid, whereas diphenylalanine synthesis and puromycin reaction were strongly inhibited by homoharringtonine. It has been proposed that the site of homoharringtonine binding on 80 S ribosomes shouldoverlap or coincide with the acceptor site of the ribosome.