Inhibition of Chloramphenicol Binding to Escherichia coli 70‐S Ribosomes by 2′(3′)‐ O ‐Aminoacyl‐dinucleoside Phosphates Derived from the Aminoacyl‐tRNA Acceptor Terminus

The effect of 2′ and 3′‐ O ‐aminoacyl‐dinucleoside phosphates cytidylyl(3′‐5′)‐2′(3′)‐ O ‐ l ‐phenylalanyladenosine (I), cytidylyl(3′‐5′)‐3′‐deoxy‐2′‐ O ‐ l ‐phenylalanyladenosine (IIa), cytidylyl(3′‐5′)‐2′‐deoxy‐3′‐ O ‐ l ‐phenylalanyladenosine (IIIa), cytidylyl(3′‐5′)‐3′‐deoxy‐2′‐ O ‐glycyladenosine (IIb), cytidylyl(3′‐5′)‐2′‐deoxy‐3′‐ O ‐glycyladenosine (IIIb), cytidylyl(3′‐5′)‐3′‐deoxy‐2′‐ O ‐ l ‐leucyladenosine (IIc), cytidylyl(3′‐5′)‐2′‐deoxy‐3′‐ O ‐ l ‐leucyladenosine (IIIc), cytidylyl(3′‐5′)‐3′‐ O ‐methyl‐2′‐ O ‐ l ‐phenylalanyladenosine (IId) and cytidylyl(3′‐5′)‐2′‐ O ‐methyl‐3′‐ O ‐ l ‐phenylalanyladenosine (IIId) as analogs of the 2′(3′)‐aminoacyl‐tRNA termini, on chloramphenicol binding to 70‐S Escherichia coli ribosomes was investigated. The association constants ( K b ) of the investigated compounds were determined by the equilibrium dialysis method. Based on the constancy of K b over the range of inhibitor concentration, it was determined that the binding site of the 2′ isomers IIa–IIc overlaps with the chloramphenicol site, whereas the variability of K b for the 3′ isomers IIIb, IIIc and especially IIIa seems to indicate that they do not achieve a complete fit. The consistently higher values of the K b values for the 3′ isomers IIIa–IIIc relative to that of the 2′ isomers IIa–IIc also indicate a stabilization of the binding of the former due to a specific interaction between its amino acid portion and a ribosomal site.