XDNA

Last updated June 16, 2024

Benzo-homologated Adenine


Benzo-homologated Thymine

Benzo-homologated Cytosine

Benzo-homologated Guanine

xDNA (also known as expanded DNA or benzo-homologated DNA) is a size-expanded nucleotide system synthesized from the fusion of a benzene ring and one of the four natural bases: adenine, guanine, cytosine, and thymine.^[1] This size expansion produces an 8 letter alphabet which has a larger information storage capacity than natural DNA's (often referred to as B-DNA in literature) 4 letter alphabet.^[2] As with normal base-pairing, A pairs with xT, C pairs with xG, G pairs with xC, and T pairs with xA. The double helix is thus 2.4Å wider than a natural double helix.^[3]^[4] While similar in structure to B-DNA, xDNA has unique absorption, fluorescence, and stacking properties.^[5]^[6]^[7]

Initially synthesized as an enzyme probe by Nelson J. Leonard's group, benzo-homologated adenine was the first base synthesized. Later, Eric T. Kool's group finished synthesizing the remaining three expanded bases, eventually followed by yDNA ("wide" DNA), another benzo-homologated nucleotide system, and naphtho-homologated xxDNA and yyDNA. xDNA is more stable when compared to regular DNA when subjected to higher temperature, and while entire strands of xDNA, yDNA, xxDNA and yyDNA exist, they are currently difficult to synthesize and maintain. Experiments with xDNA provide new insight into the behavior of natural B-DNA. The extended bases xA, xC, xG, and xT are naturally fluorescent, and single strands composed of only extended bases can recognize and bind to single strands of natural DNA, making them useful tools for studying biological systems.^[3]^[8] xDNA is most commonly formed with base pairs between a natural and expanded nucleobase, however x-nucleobases can also be paired together.^[5] Current research supports xDNA as a viable genetic encoding system in the near future.^[4]

Origins

The first nucleotide to be expanded was the purine adenine. Nelson J. Leonard and colleagues synthesized this original x-nucleotide, which was referred to as "expanded adenine". xA was used as a probe in the investigation of active sites of ATP-dependent enzymes, more specifically what modifications the substrate could take while still being functional.^[8]^[9] Almost two decades later, the other three bases were successfully expanded and later integrated into a double helix by Eric T. Kool and colleagues. Their goal was to create a synthetic genetic system which mimics and surpasses the functions of the natural genetic system,^[10] and to broaden the applications of DNA both in living cells and in experimental biochemistry. Once the expanded base set was created, the goal shifted to identifying or developing faithful replication enzymes and further optimizing the expanded DNA alphabet.^[8]

Synthesis

In benzo-homologated purines (xA and xG), the benzene ring is bound to the nitrogenous base through nitrogen-carbon (N-C) bonds. Benzo-homologated pyrimidines are formed through carbon-carbon (C-C) bonds between the base and the benzene.^[3] Thus far, x-nucleobases have been added to strands of DNA using phosphoramidite derivatives, as traditional polymerases have been unsuccessful in synthesizing strands of xDNA. X-nucleotides are poor candidates as substrates for B-DNA polymerases as their size interferes with binding at the catalytic domain. Attempts at using template-independent enzymes have been successful as they have a reduced geometric constraint for substrates. Terminal deoxynucleotidyl transferase (TdT) has been used previously to synthesize strands of bases which have been bound to fluorophores. Using TdT, up to 30 monomers can be combined to form a double-helix of xDNA, however this oligomeric xDNA appears to inhibit its own extension beyond this length due to the overwhelming hydrogen bonding. In order to minimize inhibition, xDNA can be hybridized into a regular helix.^[7]^[11]

Replication

For xDNA to be used as a substitute structure for information storage, it requires a reliable replication mechanism. Research into xDNA replication using a Klenow fragment from DNA polymerase I shows that a natural base partner is selectively added in instances of single-nucleotide insertion. However, DNA polymerase IV (Dpo4) has been able to successfully use xDNA for these types of insertions with high fidelity, making it a promising candidate for future research in extending replicates of xDNA.^[4] xDNA's mismatch sensitivity is similar to that of B-DNA.^[2]

Structure


Adenine	Thymine	Cytosine	Guanine

Size-expanded xA	Size-expanded xT	Size-expanded xC	Size-expanded xG

Similar to natural bases, x-nucleotides selectively assemble into a duplex-structure resembling B-DNA.^[4] xDNA was originally synthesized by incorporating a benzene ring into the nitrogenous base. However, other expanded bases have been able to incorporate thiophene and benzo[b]thiophene as well. xDNA and yDNA use benzene rings to widen the bases and are thus termed "benzo-homologated". Another form of expanded nucleobases known as yyDNA incorporate naphthalene into the base and are "naptho-homologated". xDNA has a rise of 3.2Å and a twist of 32°, significantly smaller than B-DNA, which has a rise of 3.3Å and a twist of 34.2°^[3] xDNA nucleotides can occur on both strands—either alone (known as "doubly expanded DNA"^[8]) or mixed with natural bases—or exclusively on one strand or the other. Similar to B-DNA, xDNA can recognize and bind complementary single-stranded DNA or RNA sequences.^[2]

Duplexes formed from xDNA are similar to natural duplexes aside from the distance between the two sugar-phosphate backbones. xDNA helices have a greater number of base pairs per turn of the helix as a result of a reduced distance between neighbour nucleotides. NMR spectra report that xDNA helices are anti-parallel, right-handed and take an anti conformation around the glycosidic bond, with a C2'-endo sugar pucker.^[5]^[11] Helices created from xDNA are more likely to take a B-helix over an A-helix conformation,^[2] and have an increased major groove width by 6.5Å (where the backbones are farthest apart) and decreased minor groove width by 5.5Å (where the backbones are closest together) compared to B-DNA. Altering groove width affects the xDNA's ability to associate with DNA-binding proteins,^[12] but as long as the expanded nucleotides are exclusive to one strand, recognition sites are sufficiently similar to B-DNA to allow bonding of transcription factors and small polyamide molecules. Mixed helices present the possibility of recognizing the four expanded bases using other DNA-binding molecules.^[11]

Properties

Expanded nucleotides and their oligomeric helices share many properties with their natural B-DNA counterparts, including their pairing preference: A with T, C with G.^[11] The various differences in chemical properties between xDNA and B-DNA support the hypothesis that the benzene ring which expands x-nucleobases is not, in fact, chemically inert.^[5] xDNA is more hydrophobic than B-DNA,^[7] and also has a smaller HOMO-LUMO gap (distance between the highest occupied molecular orbital and lowest unoccupied molecular orbital) as a result of modified saturation.^[3] xDNA has higher melting temperatures than B-DNA (a mixed decamer of xA and T has a melting temperature of 55.6 °C, 34.3 °C higher than the same decamer of A and T^[11]), and exhibits an "all-or-nothing" melting behaviour.^[2]

Conformation

Under lab conditions, xDNA orients itself in the syn conformation. This unfortunately does not expose the binding face of the xDNA nucleotides to face the neighbouring strand for binding, meaning that extra measures must be applied to alter the conformation of xDNA before attempting to form helices. However, the anti and syn orientations are practically identical energetically in expanded bases.^[9] This conformational preference is seen primarily in pyrimidines, and purines display minimal preference for orientation.^[5]

Enhanced stacking

Stacking of the nucleotides in a double helix is a major determinant of the helix's stability. With the added surface area and hydrogen available for bonding, stacking potential for the nucleobases increases with the addition of a benzene spacer. By increasing the separation between the nitrogenous bases and either sugar-phosphate backbone, the helix's stacking energy is less variable and therefore more stable. The energies for natural nucleobase pairs vary from 18 to 52 kJ/mol. This variance is only 14–40 kJ/mol for xDNA.^[8]

Due to an increased overlap between and expanded strand of DNA and its neighbouring strand, there are greater interstrand interactions in expanded and mixed helices, resulting in a significant increase in the helix's stability. xDNA has enhanced stacking abilities resultant from changes in inter- and intrastrand hydrogen bonding that arise from the addition of a benzene spacer, but expanding the bases does not alter hydrogen's contribution to the stability of the duplex. These stacking abilities are exploited by helices consisting of both xDNA and B-DNA in order to optimize the strength of the helix. Increased stacking is seen most prominently in strands consisting only of A and xA and T and xT, as T-xA has stronger stacking interactions than T-A.^[3]

The energy resultant from pyrimidines ranges from 30 to 49 kJ/mol. The range for purines is between 40-58kJ/mol. By replacing one nucleotide in a double-helix with an expanded nucleotide, the strength of the stacking interactions increases by 50%. Expanding both nucleotides results in a 90% increase in stacking strength. While xG has an overall negative effect on the binding strength of the helix, the other three expanded bases outweigh this with their positive effects. The change in energy caused by expanding the bases is mostly dependent on the rotation of the bond about the nucleobases' centers of mass, and center of mass stacking interactions improve the stacking potential of the helix.^[5] Because the size-expanded bases widen the helix, it is more thermally stable with a higher melting temperature.^[7]

Absorption

The addition of a benzene spacer in x-nucleobases affects the bases' optical absorption spectra. Time-dependent density functional theory (TDDFT) applied to xDNA revealed that the benzene component of the highest occupied molecular orbitals (HOMO) in the x-bases pins the absorption onset at an earlier point than natural bases. Another unusual feature of xDNA absorption spectra is the red-shifted excimers of xA in the low range. In terms of stacking fingerprints, there is a more pronounced hypochromicity seen in consecutive xA-T base pairs.

Implications of xDNA's altered absorption include applications in nanoelectronic technology and nanobiotechnology. The reduced spacing between x-nucleotides makes the helix stiffer, thus it is not as easily affected by substrate, electrode, and functional nanoparticle forces. Other alterations to natural nucleotides resulting in different absorption spectra will broaden these applications in the future.^[6]

Fluorescence

One unique property of xDNA is its inherent fluorescence. Natural bases can be bound directly to fluorophores for use in microarrays, in situ hybridization, and polymorphism analysis. However, these fluorescent natural bases often fail as a result of self-quenching, which diminishes their fluorescent intensity and reduces their applicability as visual DNA tags. The pi interactions between the rings in x-nucleobases result in an inherent fluorescence in the violet-blue range, with a Stokes shift between 50 and 80 nm. They also have a quantum yield in the range of 0.3–0.6. xC has the greatest fluorescent emission.^[10]^[7]

Other expanded bases

After the creation of and successful research surrounding xDNA, more forms of expanded nucleotides were investigated. yDNA is a second, similar system of nucleotides which uses a benzene ring to expand the four natural bases. xxDNA and yyDNA use naphthalene, a polycyclic molecule consisting of two hydrocarbon rings. The two rings expand the base even wider, further altering its chemical properties.

yDNA

The success and implications of xDNA prompted research to examine other factors which could alter B-DNA's chemical properties and create a new system for information storage with broader applications. yDNA also uses a benzene ring, similar to xDNA, with the only difference being the site of addition of the aromatic ring. The location of the benzene ring changes the preferred structure of the expanded helix. The altered conformation makes yDNA more similar to B-DNA in its orientation by changing the interstrand hydrogen bonds. Stability is highly dependent on the bases' rotation about the link between the base and the sugar of the backbone. yDNA's altered preference for this orientation makes it more stable overall than xDNA. The location of the benzene spacer also affects the bases' groove geometry, altering neighbour interactions. The base pairs between y-nucleotides and natural nucleotides is planar, rather than slightly twisted as with xDNA. This decreases the rise of the helix even further than achieved by xDNA.

While xDNA and yDNA are quite similar in most properties, including their increased stacking interactions, yDNA shows superior mismatch recognition. y-pyrimidines display slightly stronger stacking interactions than x-pyrimidines as a result of the distance between the two anomeric carbons, which is slightly larger in yDNA. xDNA still has stronger stacking interactions in model helices, but adding either x- or y-pyrimidines to a natural double helix strengthens the intra- and interstrand interactions, increasing overall helix stability. In the end, which of the two has the strongest overall stacking interactions is dependent on the sequence; xT and yT bind A with similar strength, but the stacking energy of yC bound to G is stronger than xC by 4kJ/mol. yDNA and other expanded bases are part of a very young field which is highly understudied. Research suggest that the ideal conformation still remains to be discovered, but knowing that the benzene location affects the orientation and structure of expanded nucleobases adds information to their future design.^[8]

yyDNA and xxDNA

Doubly-expanded (or naphtho-homologated) nucleobases incorporate a naphthalene spacer instead of a benzene ring, widening the base twice as much with its two-ringed structure. These structures (known as xxDNA and yyDNA) are 4.8Å wider than natural bases and were once again created as a result of Leonard's research on expanded adenine in ATP-dependent enzymes in 1984. No literature was published on these doubly-expanded bases for nearly three decades until 2013 when the first xxG was produced by Sharma, Lait, and Wetmore and incorporated along with xxA into a natural helix. Although very little research has been performed on xxDNA, xx-purine neighbours have already been shown to increase intrastrand stacking energy by up to 119% (as opposed to 62% in x-purines). xx-purine and pyrimidine interactions show an overall decrease in stacking energies, but the overall stability of duplexes including pyrimidines and xx-purines increases by 22%, more than twofold that of pyrimidines and x-purines.^[9]

Uses

xDNA has many applications in chemical and biological research, including expanding upon applications of natural DNA, such as scaffolding. In order to create self-assembling nanostructures, a scaffold is needed as a sort of trellis to support the growth. DNA has been used as a means to this end in the past, but expanded scaffolds make larger scaffolds for more complex self-assembly an option.^[1] xDNA's electrical conduction properties also make it a prime candidate as a molecular wire, as its π-π interactions help it efficiently conduct electricity.^[3] Its 8-letter alphabet (A, T, C, G, xA, xT, xC, xG) gives it the potential to store 2ⁿ times more states per sequence than DNA, where n is the number of bases in the sequence. For example, combining 6 nucleotides of with B-DNA yields 4096 possible sequences, whereas a combination of the same number of nucleotides created with xDNA yields 262,144 possible sequences. Additionally, xDNA can be used as a fluorescent probe at enzyme active sites, as was its original application by Leonard et al.^[2]

xDNA has also been applied to the study of protein-DNA interactions. Due to xDNA's natural fluorescing properties, it can easily be visualized in both lab and living conditions.^[5] xDNA is becoming more easy to create and oligomerize, and its high-affinity binding to complementary DNA and RNA sequences means that it can not only help locate these sequences floating around in the cell, but also when they are already interacting with other structures within the cell.^[10] xDNA also has potential applications in assays that employ TdT as it may improve reporters, and can be used as an affinity tag for interstrand bonding.^[7]

Related Research Articles

A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA and RNA. Dictated by specific hydrogen bonding patterns, "Watson–Crick" base pairs allow the DNA helix to maintain a regular helical structure that is subtly dependent on its nucleotide sequence. The complementary nature of this based-paired structure provides a redundant copy of the genetic information encoded within each strand of DNA. The regular structure and data redundancy provided by the DNA double helix make DNA well suited to the storage of genetic information, while base-pairing between DNA and incoming nucleotides provides the mechanism through which DNA polymerase replicates DNA and RNA polymerase transcribes DNA into RNA. Many DNA-binding proteins can recognize specific base-pairing patterns that identify particular regulatory regions of genes.

Deoxyribonucleic acid is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of all known organisms and many viruses. DNA and ribonucleic acid (RNA) are nucleic acids. Alongside proteins, lipids and complex carbohydrates (polysaccharides), nucleic acids are one of the four major types of macromolecules that are essential for all known forms of life.

Nucleic acids are large biomolecules that are crucial in all cells and viruses. They are composed of nucleotides, which are the monomer components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). If the sugar is ribose, the polymer is RNA; if the sugar is deoxyribose, a variant of ribose, the polymer is DNA.

Nucleotides are organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules within all life-forms on Earth. Nucleotides are obtained in the diet and are also synthesized from common nutrients by the liver.

Purine is a heterocyclic aromatic organic compound that consists of two rings fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which include substituted purines and their tautomers. They are the most widely occurring nitrogen-containing heterocycles in nature.

Pyrimidine is an aromatic, heterocyclic, organic compound similar to pyridine. One of the three diazines, it has nitrogen atoms at positions 1 and 3 in the ring. The other diazines are pyrazine and pyridazine.

Nucleobases are nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the basic building blocks of nucleic acids. The ability of nucleobases to form base pairs and to stack one upon another leads directly to long-chain helical structures such as ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). Five nucleobases—adenine (A), cytosine (C), guanine (G), thymine (T), and uracil (U)—are called primary or canonical. They function as the fundamental units of the genetic code, with the bases A, G, C, and T being found in DNA while A, G, C, and U are found in RNA. Thymine and uracil are distinguished by merely the presence or absence of a methyl group on the fifth carbon (C5) of these heterocyclic six-membered rings. In addition, some viruses have aminoadenine (Z) instead of adenine. It differs in having an extra amine group, creating a more stable bond to thymine.

<span class="mw-page-title-main">Nucleoside</span> Any of several glycosylamines comprising a nucleobase and a sugar molecule

Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase and a five-carbon sugar whereas a nucleotide is composed of a nucleobase, a five-carbon sugar, and one or more phosphate groups. In a nucleoside, the anomeric carbon is linked through a glycosidic bond to the N9 of a purine or the N1 of a pyrimidine. Nucleotides are the molecular building blocks of DNA and RNA.

In biochemistry, a ribonucleotide is a nucleotide containing ribose as its pentose component. It is considered a molecular precursor of nucleic acids. Nucleotides are the basic building blocks of DNA and RNA. Ribonucleotides themselves are basic monomeric building blocks for RNA. Deoxyribonucleotides, formed by reducing ribonucleotides with the enzyme ribonucleotide reductase (RNR), are essential building blocks for DNA. There are several differences between DNA deoxyribonucleotides and RNA ribonucleotides. Successive nucleotides are linked together via phosphodiester bonds.

A Hoogsteen base pair is a variation of base-pairing in nucleic acids such as the A•T pair. In this manner, two nucleobases, one on each strand, can be held together by hydrogen bonds in the major groove. A Hoogsteen base pair applies the N7 position of the purine base and C6 amino group, which bind the Watson–Crick (N3–C4) face of the pyrimidine base.

The replisome is a complex molecular machine that carries out replication of DNA. The replisome first unwinds double stranded DNA into two single strands. For each of the resulting single strands, a new complementary sequence of DNA is synthesized. The total result is formation of two new double stranded DNA sequences that are exact copies of the original double stranded DNA sequence.

Nucleic acid analogues are compounds which are analogous to naturally occurring RNA and DNA, used in medicine and in molecular biology research. Nucleic acids are chains of nucleotides, which are composed of three parts: a phosphate backbone, a pentose sugar, either ribose or deoxyribose, and one of four nucleobases. An analogue may have any of these altered. Typically the analogue nucleobases confer, among other things, different base pairing and base stacking properties. Examples include universal bases, which can pair with all four canonical bases, and phosphate-sugar backbone analogues such as PNA, which affect the properties of the chain . Nucleic acid analogues are also called xeno nucleic acids and represent one of the main pillars of xenobiology, the design of new-to-nature forms of life based on alternative biochemistries.

Nucleic acid structure refers to the structure of nucleic acids such as DNA and RNA. Chemically speaking, DNA and RNA are very similar. Nucleic acid structure is often divided into four different levels: primary, secondary, tertiary, and quaternary.

Nucleic acid secondary structure is the basepairing interactions within a single nucleic acid polymer or between two polymers. It can be represented as a list of bases which are paired in a nucleic acid molecule. The secondary structures of biological DNAs and RNAs tend to be different: biological DNA mostly exists as fully base paired double helices, while biological RNA is single stranded and often forms complex and intricate base-pairing interactions due to its increased ability to form hydrogen bonds stemming from the extra hydroxyl group in the ribose sugar.

In molecular biology, complementarity describes a relationship between two structures each following the lock-and-key principle. In nature complementarity is the base principle of DNA replication and transcription as it is a property shared between two DNA or RNA sequences, such that when they are aligned antiparallel to each other, the nucleotide bases at each position in the sequences will be complementary, much like looking in the mirror and seeing the reverse of things. This complementary base pairing allows cells to copy information from one generation to another and even find and repair damage to the information stored in the sequences.

In the fields of geometry and biochemistry, a triple helix is a set of three congruent geometrical helices with the same axis, differing by a translation along the axis. This means that each of the helices keeps the same distance from the central axis. As with a single helix, a triple helix may be characterized by its pitch, diameter, and handedness. Examples of triple helices include triplex DNA, triplex RNA, the collagen helix, and collagen-like proteins.

Non-canonical base pairs are planar hydrogen bonded pairs of nucleobases, having hydrogen bonding patterns which differ from the patterns observed in Watson-Crick base pairs, as in the classic double helical DNA. The structures of polynucleotide strands of both DNA and RNA molecules can be understood in terms of sugar-phosphate backbones consisting of phosphodiester-linked D 2’ deoxyribofuranose sugar moieties, with purine or pyrimidine nucleobases covalently linked to them. Here, the N9 atoms of the purines, guanine and adenine, and the N1 atoms of the pyrimidines, cytosine and thymine, respectively, form glycosidic linkages with the C1’ atom of the sugars. These nucleobases can be schematically represented as triangles with one of their vertices linked to the sugar, and the three sides accounting for three edges through which they can form hydrogen bonds with other moieties, including with other nucleobases. The side opposite to the sugar linked vertex is traditionally called the Watson-Crick edge, since they are involved in forming the Watson-Crick base pairs which constitute building blocks of double helical DNA. The two sides adjacent to the sugar-linked vertex are referred to, respectively, as the Sugar and Hoogsteen edges.

<span class="mw-page-title-main">Hachimoji DNA</span> Synthetic DNA

Hachimoji DNA is a synthetic nucleic acid analog that uses four synthetic nucleotides in addition to the four present in the natural nucleic acids, DNA and RNA. This leads to four allowed base pairs: two unnatural base pairs formed by the synthetic nucleobases in addition to the two normal pairs. Hachimoji bases have been demonstrated in both DNA and RNA analogs, using deoxyribose and ribose respectively as the backbone sugar.

This glossary of cellular and molecular biology is a list of definitions of terms and concepts commonly used in the study of cell biology, molecular biology, and related disciplines, including molecular genetics, biochemistry, and microbiology. It is split across two articles:

This glossary of cellular and molecular biology is a list of definitions of terms and concepts commonly used in the study of cell biology, molecular biology, and related disciplines, including genetics, biochemistry, and microbiology. It is split across two articles:

References

1 2 Lynch SR, Liu H, Gao J, Kool ET (November 2006). "Toward a designed, functioning genetic system with expanded-size base pairs: solution structure of the eight-base xDNA double helix". Journal of the American Chemical Society. 128 (45): 14704–11. doi:10.1021/ja065606n. PMC 2519095 . PMID 17090058.
1 2 3 4 5 6 Gao J, Liu H, Kool ET (May 2005). "Assembly of the complete eight-base artificial genetic helix, xDNA, and its interaction with the natural genetic system". Angewandte Chemie. 44 (20): 3118–22. doi:10.1002/anie.200500069. PMID 15834852.
1 2 3 4 5 6 7 Fuentes-Cabrera M, Zhao X, Kent PR, Sumpter BG (August 2007). "Electronic structure of xDNA". The Journal of Physical Chemistry B. 111 (30): 9057–61. doi:10.1021/jp0729056. PMID 17650925.
1 2 3 4 Krueger AT, Lu H, Højland T, Liu H, Gao J, Kool ET (2008-09-01). "Towards the replication of xDNA, a size-expanded unnatural genetic system". Nucleic Acids Symposium Series. 52 (1): 455–6. doi: 10.1093/nass/nrn231 . PMID 18776450.
1 2 3 4 5 6 7 McConnell TL, Wetmore SD (March 2007). "How do size-expanded DNA nucleobases enhance duplex stability? Computational analysis of the hydrogen-bonding and stacking ability of xDNA bases". The Journal of Physical Chemistry B. 111 (11): 2999–3009. doi:10.1021/jp0670079. PMID 17388411.
1 2 Varsano D, Garbesi A, Di Felice R (December 2007). "Ab initio optical absorption spectra of size-expanded xDNA base assemblies". The Journal of Physical Chemistry B. 111 (50): 14012–21. doi:10.1021/jp075711z. PMID 18034470.
1 2 3 4 5 6 Jarchow-Choy SK, Krueger AT, Liu H, Gao J, Kool ET (March 2011). "Fluorescent xDNA nucleotides as efficient substrates for a template-independent polymerase". Nucleic Acids Research. 39 (4): 1586–94. doi:10.1093/nar/gkq853. PMC 3045586 . PMID 20947563.
1 2 3 4 5 6 Lait LA, Rutledge LR, Millen AL, Wetmore SD (October 2008). "yDNA versus xDNA pyrimidine nucleobases: computational evidence for dependence of duplex stability on spacer location". The Journal of Physical Chemistry B. 112 (39): 12526–36. doi:10.1021/jp805547p. PMID 18771305.
1 2 3 Sharma P, Lait LA, Wetmore SD (October 2013). "Exploring the limits of nucleobase expansion: computational design of naphthohomologated (xx-) purines and comparison to the natural and xDNA purines". Physical Chemistry Chemical Physics. 15 (37): 15538–49. Bibcode:2013PCCP...1515538S. doi:10.1039/c3cp52656a. PMID 23942832.
1 2 3 Krueger AT, Lu H, Lee AH, Kool ET (February 2007). "Synthesis and properties of size-expanded DNAs: toward designed, functional genetic systems". Accounts of Chemical Research. 40 (2): 141–50. doi:10.1021/ar068200o. PMC 2539066 . PMID 17309194.
1 2 3 4 5 Heckel A (June 2004). "A new DNA analogue with expanded size and scope". ChemBioChem. 5 (6): 765–7. doi:10.1002/cbic.200400001. PMID 15174157. S2CID 26157871.
↑ Varghese MK, Thomas R, Unnikrishnan NV, Sudarsanakumar C (May 2009). "Molecular dynamics simulations of xDNA". Biopolymers. 91 (5): 351–60. doi:10.1002/bip.21137. PMID 19137576. S2CID 38901164.

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[:7-1] 1 2 Lynch SR, Liu H, Gao J, Kool ET (November 2006). "Toward a designed, functioning genetic system with expanded-size base pairs: solution structure of the eight-base xDNA double helix". Journal of the American Chemical Society. 128 (45): 14704–11. doi:10.1021/ja065606n. PMC 2519095 . PMID 17090058.

[:0-2] 1 2 3 4 5 6 Gao J, Liu H, Kool ET (May 2005). "Assembly of the complete eight-base artificial genetic helix, xDNA, and its interaction with the natural genetic system". Angewandte Chemie. 44 (20): 3118–22. doi:10.1002/anie.200500069. PMID 15834852.

[:3-3] 1 2 3 4 5 6 7 Fuentes-Cabrera M, Zhao X, Kent PR, Sumpter BG (August 2007). "Electronic structure of xDNA". The Journal of Physical Chemistry B. 111 (30): 9057–61. doi:10.1021/jp0729056. PMID 17650925.

[:4-4] 1 2 3 4 Krueger AT, Lu H, Højland T, Liu H, Gao J, Kool ET (2008-09-01). "Towards the replication of xDNA, a size-expanded unnatural genetic system". Nucleic Acids Symposium Series. 52 (1): 455–6. doi: 10.1093/nass/nrn231 . PMID 18776450.

[:1-5] 1 2 3 4 5 6 7 McConnell TL, Wetmore SD (March 2007). "How do size-expanded DNA nucleobases enhance duplex stability? Computational analysis of the hydrogen-bonding and stacking ability of xDNA bases". The Journal of Physical Chemistry B. 111 (11): 2999–3009. doi:10.1021/jp0670079. PMID 17388411.

[:10-6] 1 2 Varsano D, Garbesi A, Di Felice R (December 2007). "Ab initio optical absorption spectra of size-expanded xDNA base assemblies". The Journal of Physical Chemistry B. 111 (50): 14012–21. doi:10.1021/jp075711z. PMID 18034470.

[:2-7] 1 2 3 4 5 6 Jarchow-Choy SK, Krueger AT, Liu H, Gao J, Kool ET (March 2011). "Fluorescent xDNA nucleotides as efficient substrates for a template-independent polymerase". Nucleic Acids Research. 39 (4): 1586–94. doi:10.1093/nar/gkq853. PMC 3045586 . PMID 20947563.

[:5-8] 1 2 3 4 5 6 Lait LA, Rutledge LR, Millen AL, Wetmore SD (October 2008). "yDNA versus xDNA pyrimidine nucleobases: computational evidence for dependence of duplex stability on spacer location". The Journal of Physical Chemistry B. 112 (39): 12526–36. doi:10.1021/jp805547p. PMID 18771305.

[:6-9] 1 2 3 Sharma P, Lait LA, Wetmore SD (October 2013). "Exploring the limits of nucleobase expansion: computational design of naphthohomologated (xx-) purines and comparison to the natural and xDNA purines". Physical Chemistry Chemical Physics. 15 (37): 15538–49. Bibcode:2013PCCP...1515538S. doi:10.1039/c3cp52656a. PMID 23942832.

[:9-10] 1 2 3 Krueger AT, Lu H, Lee AH, Kool ET (February 2007). "Synthesis and properties of size-expanded DNAs: toward designed, functional genetic systems". Accounts of Chemical Research. 40 (2): 141–50. doi:10.1021/ar068200o. PMC 2539066 . PMID 17309194.

[:8-11] 1 2 3 4 5 Heckel A (June 2004). "A new DNA analogue with expanded size and scope". ChemBioChem. 5 (6): 765–7. doi:10.1002/cbic.200400001. PMID 15174157. S2CID 26157871.

[12] Varghese MK, Thomas R, Unnikrishnan NV, Sudarsanakumar C (May 2009). "Molecular dynamics simulations of xDNA". Biopolymers. 91 (5): 351–60. doi:10.1002/bip.21137. PMID 19137576. S2CID 38901164.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]