WHY PENTOSE-NUCLEIC-ACID AND NOT HEXOSE-N UCLEIC-ACID - PURINE-PURINEPAIRING IN HOMO-DNA - GUANINE, ISOGUANINE, 2,6-DIAMINOPURINE, AND XANTHINE

This paper concludes the series of reports in this journal [1-4] on th e chemistry of homo-DNA, the constitutionally simplified model system of hexopyranosyl-(6' --> 4')-oligonucleotide systems studied in our la boratory as potentially natural-nucleic-acid alternatives in the conte xt of a chemical aetiology of nucleic-acid structure. The report descr ibes the synthesis and pairing properties of homo-DNA oligonucleotides which contain as nucleobases exclusively purines, and gives, together with part III of the series [3], a survey of what we know today about purine-purine pairing in homo-DNA. In addition, the paper discusses t hose aspects of the chemistry of homo-DNA which, we think, influence t he way how some of the structural features of DNA (and RNA) are to be interpreted on a qualitative level. Purine-purine pairing occurs in th e homo-DNA domain in great variety. Most prominent is a novel tridenta te Watson-Crick pair between guanine and isoguanine, as well as one be tween 2,6-diaminopurine and xanthine, both giving rise to very stable duplexes containing the all-purine strands in antiparallel orientation . For the guanine-isoguanine pair, constitutional assignment is based on temperature-dependent UV and CD spectroscopy of various guanine-and isoguanine-containing duplexes in comparison with duplexes known to b e paired in the reverse-Hoogsteen mode. The assignment is supported by the characteristic changes observed in pairing behavior when guanine is replaced by 7-carbaguanine. Isoguanine and 2,6-diaminopurine also h ave the capability of self-pairing in the reverse-Hoogsteen mode, as p reviously observed for adenine and guanine [3]. In this type of pairin g, the purine bases that contain an amino group in the 6-position (ade nine, a,6-diaminopurine, and isoguanine) behave interchangeably. Fig. 36 provides an overall survey of the relative strength of pairing in a ll possible purine-purine combinations. Watson-Crick pairing of isogua nine with guanine demands the former to participate in its 3H-tautomer ic form; hitherto this specific tautomer had not been considered in th e pairing chemistry of isoguanine. Whereas (cumulative) purine-purine pairing in DNA (reverse-Hoogsten or Hoogsteen) seems to occur in tripl exes and tetraplexes only, its occurrence in duplexes is a characteris tic feature of homo-DNA chemistry. The occurrence of purine-purine Wat son-Crick base pairs is probably a consequence of homo-DNA's quasi-lin ear ladder structure [1][4]. In a double helix, the distance between t he two sugar C atoms, on which a base pair is anchored, is expected to be constrained by the dimensions of the helix; in a linear duplex, ho wever, there would be no restrictions with regard to base-pair length. Homo-DNA's ladder-like model also allows one to recognize one of the reasons why nucleic-acid duplexes prefer to pair in antiparallel, rath er than parallel strand orientation: in homo-DNA duplexes: (averaged) backbone and base pair axes are strongly inclined toward one another [ 4]; the stronger this inclination, the higher the preference for antip arallel strand orientation is expected to be (Fiq. 16). In retrospect, homo-DNA turns out to be one of the first artificial oligonucleotide systems (cf. Footnote 6.5) to demonstrate in a comprehensive way that informational base pairing involving purines and pyrimidines is not a capability unique to ribofuranosyl systems. Stability and helical shap e of pairing complexes are not necessary conditions of one another; it is the potential for extensive conformational cooperativity of the ba ckbone structure with respect to the constellational demands of base p airing and base stacking that determines whether or not a given type o f base-carrying backbone structure is an informational pairing system. From the viewpoint of the chemical aetiology of nucleic-acid structur e, which inspired our investigations on hexopyranosyl-(6' --> 4')-olig onucleotide systems in the first place, the work on homo-DNA is only a n extensive model study, because homo-DNA is not to be considered a po tential natural-nucleic-acid alternative. In retrospect. it seems fort unate that the model study was carried out, because without it we coul d hardly have comprehended the pairing behavior of the proper nucleic- acid alternatives which we have studied later and which will be discus sed in Part VI of this series.