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Influence of the incorporation of a cyclohexenyl nucleic acid (CeNA) residue onto the sequence d(CGCGAATTCGCG).

Robeyns K, Herdewijn P, Van Meervelt L - Nucleic Acids Res. (2007)

Bottom Line: As it has been demonstrated that even a single cyclohexenyl nucleoside, when incorporated in an oligonucleotide, can have a profound effect on the biological activity of the oligonucleotide, further research is warranted to study the complex of such oligonucleotides with target proteins.The cyclohexene ring adopts the (2)E-conformation allowing a better incorporation of the residue in the dodecamer sequence.The crystal packing is stabilized by cobalt hexamine residues and belongs to space group P222(1), never before reported for nucleic acids.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Katholieke Universiteit Leuven, Biomolecular Architecture and BioMacS, Celestijnenlaan 200F, B-3001 Leuven, Belgium.

ABSTRACT
Cyclohexene nucleic acids (CeNA), which are characterized by the presence of a cyclohexene moiety instead of a natural (deoxy)ribose sugar, are known to increase the thermal and enzymatic stability when incorporated in RNA oligonucleotides. As it has been demonstrated that even a single cyclohexenyl nucleoside, when incorporated in an oligonucleotide, can have a profound effect on the biological activity of the oligonucleotide, further research is warranted to study the complex of such oligonucleotides with target proteins. In order to analyse the influence of CeNA residues onto the helix conformation and hydration of natural nucleic acid structures, a cyclohexenyl-adenine building block (xAr) was incorporated into the Dickerson sequence CGCGA(xAr)TTCGCG. The crystal structure of this sequence determined to a resolution of 1.90 A. The global helix belongs to the B-type family and shows a water spine, which is partially broken up by the apolar cyclohexene residue. The cyclohexene ring adopts the (2)E-conformation allowing a better incorporation of the residue in the dodecamer sequence. The crystal packing is stabilized by cobalt hexamine residues and belongs to space group P222(1), never before reported for nucleic acids.

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Stick representation and electron density of residues 6 (xAr) (CeNA) and T7. The CeNA sugar ring adopts the 2E envelope conformation rather than the 2H3 half-chair conformation. The C3′ atom of the CeNA moiety is pushed into the plane formed by the double bond in order to prevent further stretching of the intra-strand phosphate distance, now 7.2 Å, and to preserve the global B-type conformation. Electron density maps are calculated with refined phases and contoured at 1.1σ above the average background.
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Figure 3: Stick representation and electron density of residues 6 (xAr) (CeNA) and T7. The CeNA sugar ring adopts the 2E envelope conformation rather than the 2H3 half-chair conformation. The C3′ atom of the CeNA moiety is pushed into the plane formed by the double bond in order to prevent further stretching of the intra-strand phosphate distance, now 7.2 Å, and to preserve the global B-type conformation. Electron density maps are calculated with refined phases and contoured at 1.1σ above the average background.

Mentions: The ring puckering of the five-membered deoxyribonucleotides ranges from C2′-endo over C1′-exo and C4′-exo to C3′-endo for both duplex One and duplex Two. In order to minimize the deviation from the global B-type helix, the cyclohexene ring is forced into the 2E-envelope conformation, rather than the suggested 2H3 half-chair conformation. The average intra-strand phosphate distance in B-type DNA is ∼7.0 Å (24). The C3′ atom of the CeNA residue is pushed into the plane, formed by the double bond, to reduce the intra-strand phosphate distance to the average value found in B-type DNA and to preserve the global B-type helix. The intra-stand phosphate distance between the phosphate atom from the CeNA residue and phosphate atom attached to its 3′-end is 7.2 Å for both duplexes One and Two (Figure 3).Figure 3.


Influence of the incorporation of a cyclohexenyl nucleic acid (CeNA) residue onto the sequence d(CGCGAATTCGCG).

Robeyns K, Herdewijn P, Van Meervelt L - Nucleic Acids Res. (2007)

Stick representation and electron density of residues 6 (xAr) (CeNA) and T7. The CeNA sugar ring adopts the 2E envelope conformation rather than the 2H3 half-chair conformation. The C3′ atom of the CeNA moiety is pushed into the plane formed by the double bond in order to prevent further stretching of the intra-strand phosphate distance, now 7.2 Å, and to preserve the global B-type conformation. Electron density maps are calculated with refined phases and contoured at 1.1σ above the average background.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2275148&req=5

Figure 3: Stick representation and electron density of residues 6 (xAr) (CeNA) and T7. The CeNA sugar ring adopts the 2E envelope conformation rather than the 2H3 half-chair conformation. The C3′ atom of the CeNA moiety is pushed into the plane formed by the double bond in order to prevent further stretching of the intra-strand phosphate distance, now 7.2 Å, and to preserve the global B-type conformation. Electron density maps are calculated with refined phases and contoured at 1.1σ above the average background.
Mentions: The ring puckering of the five-membered deoxyribonucleotides ranges from C2′-endo over C1′-exo and C4′-exo to C3′-endo for both duplex One and duplex Two. In order to minimize the deviation from the global B-type helix, the cyclohexene ring is forced into the 2E-envelope conformation, rather than the suggested 2H3 half-chair conformation. The average intra-strand phosphate distance in B-type DNA is ∼7.0 Å (24). The C3′ atom of the CeNA residue is pushed into the plane, formed by the double bond, to reduce the intra-strand phosphate distance to the average value found in B-type DNA and to preserve the global B-type helix. The intra-stand phosphate distance between the phosphate atom from the CeNA residue and phosphate atom attached to its 3′-end is 7.2 Å for both duplexes One and Two (Figure 3).Figure 3.

Bottom Line: As it has been demonstrated that even a single cyclohexenyl nucleoside, when incorporated in an oligonucleotide, can have a profound effect on the biological activity of the oligonucleotide, further research is warranted to study the complex of such oligonucleotides with target proteins.The cyclohexene ring adopts the (2)E-conformation allowing a better incorporation of the residue in the dodecamer sequence.The crystal packing is stabilized by cobalt hexamine residues and belongs to space group P222(1), never before reported for nucleic acids.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Katholieke Universiteit Leuven, Biomolecular Architecture and BioMacS, Celestijnenlaan 200F, B-3001 Leuven, Belgium.

ABSTRACT
Cyclohexene nucleic acids (CeNA), which are characterized by the presence of a cyclohexene moiety instead of a natural (deoxy)ribose sugar, are known to increase the thermal and enzymatic stability when incorporated in RNA oligonucleotides. As it has been demonstrated that even a single cyclohexenyl nucleoside, when incorporated in an oligonucleotide, can have a profound effect on the biological activity of the oligonucleotide, further research is warranted to study the complex of such oligonucleotides with target proteins. In order to analyse the influence of CeNA residues onto the helix conformation and hydration of natural nucleic acid structures, a cyclohexenyl-adenine building block (xAr) was incorporated into the Dickerson sequence CGCGA(xAr)TTCGCG. The crystal structure of this sequence determined to a resolution of 1.90 A. The global helix belongs to the B-type family and shows a water spine, which is partially broken up by the apolar cyclohexene residue. The cyclohexene ring adopts the (2)E-conformation allowing a better incorporation of the residue in the dodecamer sequence. The crystal packing is stabilized by cobalt hexamine residues and belongs to space group P222(1), never before reported for nucleic acids.

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