Intramolecular acyl migration in adenosine derivatives.

Abstract

with the elongation of the polypeptide chain. There is considerable uncertainty regarding the position of both the peptidyl group and the amino acyl group on the terminal adenosine of tratnsfer RNA. It has been shown that the amino acid is able to migrate from the 2' to the 3' hydroxyl groups under mild conditions.2 This migration occurs because of the close proximity of the two hydroxyl groups on the same side of the furanose ring of ribose. In view of the close proximity of the two cis hydroxyl groups, an alternative formulation can be proposed for the unit step associated with peptide bond formation. This is a two-step mechanism in which the peptidyl group is initially transferred from the adenosine of one transfer RNA to the adenosine of the adjoining transfer RNA which already is aminoacylated. Such a mechanism would lead to an intermediate in which the terminal adenosine may have a peptidyl group esterified on the 2' position and an amino acid on the 3' position (or vice versa). The initial transesterification step would then be followed by an intramolecular rearrangement in which the peptidyl group is transferred from the 2' hydroxyl to the amino group of the amino acid on the 3' position. In this latter step, a nucleophilic attack by the a-amino group of the amirmo acid on the first carbonyl group of the peptidyl chain would result in peptide bond formationi (cf. Fig. 3b). In exploring this hypothetical mechanism, we have designed some chemical experiments to test the feasibility of the second step in the process described above. Thus we have prepared 2',3'-diphenylalanyl adenosine aind have shown that this will lead to the synthesis of the dipeptide phenylalanyl phenylalanine. A second set of experiments has been carried out with derivatives of the antibiotic puromnycini, ani analogue of the terminal adenosine of trainsfer RNA. We have showni that 2'-O-acetyl puroniyciii is converted via aii initramolecular acetyl transfer reactioii to the aminoacetylated derivative of puromycin. Materials and Methods.-A n-umber of derivatives of adenosine and of puromycin were