The origin of the RNA world is not easily understood, as effective prebiotic syntheses of the components of RNA, the beta-ribofuranoside-5'-phosphates, are hard to envisage. Recognition of this difficulty has led to the proposal that other genetic systems, the components of which are more easily formed, may have preceded RNA. This raises the question of how transitions between one genetic system and another could occur. Peptide nucleic acid (PNA) resembles RNA in its ability to form double-helical complexes stabilized by Watson-Crick hydrogen bonding between adenine and thymine and between cytosine and guanine, but has a backbone that is held together by amide rather than by phosphodiester bonds. Oligonucleotides bases on RNA are known to act as templates that catalyse the non-enzymatic synthesis of their complements from activated mononucleotides, we now show that RNA oligonucleotides facilitate the synthesis of complementary PNA strands and vice versa. This suggests that a transition between different genetic systems can occur without loss of information.

Abstract. Treatment of relatively concentrated aqueous solutions of O-phospho-serine (50 mM), aspartic acid (100 mM) or glutamic acid (100 mM) with carbonyldiimidazole leads to the formation of an activated intermediate that oligomerizes efficiently. When the concentration of amino acid is reduced tenfold, few long oligomers can be detected. Positively-charged cetyltrimethyl ammonium bromide micelles concentrate the negatively-charged activated intermediates of the amino acids at their surfaces and catalyze efficient oligomerization even from dilute solutions.

Nucleotide coupling was investigated in reverse micelles formed by (cety1)trimethylammonium bromide (CTAB), in hexane/pentan-1-01. In particular, the coupling of 2'-deoxy-5'-0-methylcytidine 3'-0-phosphate, prepared by phosphoramidite chemistry, with 5'-amino-5'-deoxythymidine was studied in the presence of a H20-soluble carbodiimide at w, = 11 and 22 (w, = [H,O]/[CTAB]). The effect of w, on the reaction rate was investigated. A solid-phase strategy was developed for the synthesis of 2'-deoxy-5'-0-methyl-cytidyl-(3'-5')-5'amino-5'-deoxythymidine. The nucleotide coupling yielding the expected product occurred readily in reverse micelles. Nucleotide coupling is thus possible in reverse micelles, and this is discussed in connection with the micellar self-replication program.

Oligomers of the negatively-charged amino acids, glutamic acid, aspartic acid, and O-phospho-L-serine are adsorbed by hydroxylapatite and illite with affinities that increase with oligomer length. In the case of oligo-glutamic acids adsorbed on hydroxylapatite, addition of an extra residue results in an approximately four-fold increase in the strength of adsorption. Oligomers much longer than the 7-mer are retained tenaciously by the mineral. Repeated incubation of short oligo-glutamic acids adsorbed on hydroxylapatite or illite with activated monomer leads to the accumulation of oligomers at least 45 units long. The corresponding reactions of aspartic acid and O-phospho-L-serine on hydroxylapatite are less effective in generating long oligomers, while illite fails to accumulate substantial amounts of long oligomers of aspartic acid or of O-phospho-L-serine.

The coupling between the tri(deoxynucleotides) d[(MeO)C‐G‐Ap] (1) and d[(NH2)Td5′‐C‐G‐] (2) to yield the phosphoramidate‐linked (hexadeoxy‐nucleotide) d[(MeO)C‐G‐Anh5′Td5′‐C‐G] (3) was investigated both in aqueous solution and in reverse micelles constituted of CTAB (cetyl(trimethyl)ammonium bromide) in hexane/pentan‐1‐ol 9:1. No siginificant difference was found concerning the yield and the kinetics of the reaction in the two systems. The coupling between 1 and 2 was also carried out in the presence of the template d[(MeO)C‐G‐A‐T‐C‐G] (4), an analogue of 3, so as to reproduce the conditions of template‐directed self replication. It was shown that the trinucleotide coupling in the presence of a template obeys the so‐called square‐root law both in H2O and in reverse micelles. No significant difference of the time course of the reaction in H2O and in reverse micelles was observed. This shows that self‐replication of oligonucleotides occurs within geometrically bounded structures, which represents a step forward in the mimicking of minimal life processes.