Chemical Etiology of Nucleic Acid Structure: The Pentulofuranosyl Oligonucleotide Systems: The (1′→3′)‐β‐L‐Ribulo, (4′→3′)‐α‐L‐Xylulo, and (1′→3′)‐α‐L‐Xylulo Nucleic Acids

Abstract

Under potentially prebiotic scenarios, ribose (pentose), the component of RNA is formed in meager amounts, as opposed to ribulose and xylulose (pentuloses). Consequently, replacement of ribose in RNA, with pentulose sugars, gives rise to prospective oligonucleotide candidates that are potentially prebiotic structural variants of RNA that could be formed by the same type of chemical pathways that gave rise to RNA from ribose. The potentially natural alternative (1'→3')-ribulo oligonucleotides and (4'→3')- and (1'→3')-xylulo oligonucleotides consisting of adenine and thymine were synthesized and found to exhibit no self-pairing or cross-pairing with RNA. This signifies that even though pentulose sugars may have been abundant in a prebiotic scenario, the pentulose nucleic acids (NAs), if and when formed, would not have been competitors of RNA, or interfered with the emergence of RNA as a functional informational system. The reason for the lack of base pairing in pentulose NA highlights the contrasting and central role played by the furanosyl ring in RNA and pentulose NA, enabling and optimizing the base pairing in RNA, while impeding it in pentulose NA.

Chimeric XNA: An Unconventional Design for Orthogonal Informational Systems

“…The same behavior was observed, when DNA(A) was substituted for RNA in duplex 1 , leading to the alternating chimeric self‐complementary sequence d( x t A) 8 , forming stable duplex 3 (Table , Supporting Information Figure S29b). This suggested that the (4′,3′)‐xyluloNA units when placed in a specific arrangement with RNA in a chimeric strand, were pairing with a complementary RNA(A) or DNA(A) unit leading to chimeric‐duplex formation, even though the individual homogeneous sequences of xyluloNA( x t ) does not pair with RNA(A) or DNA(A) . Interestingly, the reverse xylulo‐purine and ribo‐pyrimidine combination in oligomer r( x a T) 8 ( 2 ) and other various alternating non‐self‐complementary xyluloNA( x n )‐RNA(N) chimeric sequences formed no self‐ or cross‐pairing stable duplexes (Supporting Table S5).…”

“…Therefore, it is not surprising that XNAs which lack (or have weak) base pairing properties are rarely investigated further . In our recent work, within the context of oligonucleotides derived from the structural neighborhood of RNA, we investigated the base pairing properties of pentulose‐derived oligonucleotides (Figure ): β‐ l ‐ribuloNA ( r n , an isomer of RNA with l ‐ribulose in place of d ‐ribose) and α‐ l ‐xyluloNA ( x n , an isomer of RNA with l ‐xylulose in place of d ‐ribose), and found them to be devoid of base pairing capacity . We observed that one or two insertions of xyluloNA mononucleotides into RNA dramatically weakened or destroyed duplex formation capabilities of the modified RNA sequences .…”

“…In our recent work, within the context of oligonucleotides derived from the structural neighborhood of RNA, we investigated the base pairing properties of pentulose‐derived oligonucleotides (Figure ): β‐ l ‐ribuloNA ( r n , an isomer of RNA with l ‐ribulose in place of d ‐ribose) and α‐ l ‐xyluloNA ( x n , an isomer of RNA with l ‐xylulose in place of d ‐ribose), and found them to be devoid of base pairing capacity . We observed that one or two insertions of xyluloNA mononucleotides into RNA dramatically weakened or destroyed duplex formation capabilities of the modified RNA sequences . A similar behavior was observed when inserting ribuloNA units into RNA for this study (Supporting Table S6, entries 12–19), reinforcing the view that pentulose‐nucleotides compromise the base pairing of RNA.…”

“…A similar behavior was observed when inserting ribuloNA units into RNA for this study (Supporting Table S6, entries 12–19), reinforcing the view that pentulose‐nucleotides compromise the base pairing of RNA. However, when we designed oligonucleotide sequences containing strictly alternating pentuloseNA‐ and RNA‐nucleotide units (which were synthesized in the context of understanding the difficulties and the low yields encountered when synthesizing full‐pentuloseNA oligomers), and investigated their base pairing potential, we observed surprising base pairing behavior that led us to reevaluate our previous assessment of the pentuloseNA‐RNA chimeric systems. The results described below demonstrate that the strategic incorporation of XNAs (with no or weak hybridization properties with themselves and with RNA/DNA) into RNA (rN) and DNA (dN) in a specific pattern (Scheme ) can create chimeric‐XNA‐systems with enhanced orthogonal base pairing properties.…”

Orotidine‐Containing RNA: Implications for the Hierarchical Selection (Systems Chemistry Emergence) of RNA

“…They include, predominantly, the stability of the nucleobases and the nucleosides at each level of transformation among many other factors, such as information storage, information transfer, and duplex‐stability . Such analyses for nucleobases would be valid for all the other prebiotically plausible components (sugars and linkers) of RNA as has been discussed by Eschenmoser (for the hexose‐versus‐pentose and pyranose‐versus‐furanose sugars), by us (for the pentuloses‐versus‐pentoses), by Westheimer (for phosphates versus other possibilities), and by Usher (for selection of 3′,5′‐linkages over 2′,5′‐linkages).…”