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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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Related in: MedlinePlus

Schematic representation of the water network observed in the minor groove of the modified Dickerson sequence CGCGA(xAr)TTCGCG. This figure is to be compared with figure 5 in Shui et al. (5) where a similar illustration is shown for the high-resolution structure (NDB code BDL084). On the left duplex One is shown, on the right duplex Two. Missing water atoms, compared to the water-spine found in the high-resolution structure are indicated with X, symmetry generated residues and water atoms are indicated with *. Notice in particular the presence of the Co(NH3)6 residues, which stabilize the water spine in duplex Two. The water spine in duplex One and duplex Two stretches symmetrically to either side of the duplex, with the central water molecules (O3 and O6) being positioned on a crystallographic 2-fold axis.
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Figure 5: Schematic representation of the water network observed in the minor groove of the modified Dickerson sequence CGCGA(xAr)TTCGCG. This figure is to be compared with figure 5 in Shui et al. (5) where a similar illustration is shown for the high-resolution structure (NDB code BDL084). On the left duplex One is shown, on the right duplex Two. Missing water atoms, compared to the water-spine found in the high-resolution structure are indicated with X, symmetry generated residues and water atoms are indicated with *. Notice in particular the presence of the Co(NH3)6 residues, which stabilize the water spine in duplex Two. The water spine in duplex One and duplex Two stretches symmetrically to either side of the duplex, with the central water molecules (O3 and O6) being positioned on a crystallographic 2-fold axis.

Mentions: In Figure 5, the schematic hydrogen network in the minor groove is shown. This schematic representation of the water network is to be compared with a similar illustration for the high-resolution structure [figure 5 in Shui et al. (5); NDB code BDL084]. When comparing both figures it is clear that the water spine is partially preserved in the modified duplexes (missing water molecules in the water spine of the modified dodecamer are indicated with X. Moreover when superposing the modified duplexes onto the high-resolution structure it is unmistakable that the water molecules occupy similar sites, despite the introduced modification (Figure 4).Figure 4.


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)

Schematic representation of the water network observed in the minor groove of the modified Dickerson sequence CGCGA(xAr)TTCGCG. This figure is to be compared with figure 5 in Shui et al. (5) where a similar illustration is shown for the high-resolution structure (NDB code BDL084). On the left duplex One is shown, on the right duplex Two. Missing water atoms, compared to the water-spine found in the high-resolution structure are indicated with X, symmetry generated residues and water atoms are indicated with *. Notice in particular the presence of the Co(NH3)6 residues, which stabilize the water spine in duplex Two. The water spine in duplex One and duplex Two stretches symmetrically to either side of the duplex, with the central water molecules (O3 and O6) being positioned on a crystallographic 2-fold axis.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 5: Schematic representation of the water network observed in the minor groove of the modified Dickerson sequence CGCGA(xAr)TTCGCG. This figure is to be compared with figure 5 in Shui et al. (5) where a similar illustration is shown for the high-resolution structure (NDB code BDL084). On the left duplex One is shown, on the right duplex Two. Missing water atoms, compared to the water-spine found in the high-resolution structure are indicated with X, symmetry generated residues and water atoms are indicated with *. Notice in particular the presence of the Co(NH3)6 residues, which stabilize the water spine in duplex Two. The water spine in duplex One and duplex Two stretches symmetrically to either side of the duplex, with the central water molecules (O3 and O6) being positioned on a crystallographic 2-fold axis.
Mentions: In Figure 5, the schematic hydrogen network in the minor groove is shown. This schematic representation of the water network is to be compared with a similar illustration for the high-resolution structure [figure 5 in Shui et al. (5); NDB code BDL084]. When comparing both figures it is clear that the water spine is partially preserved in the modified duplexes (missing water molecules in the water spine of the modified dodecamer are indicated with X. Moreover when superposing the modified duplexes onto the high-resolution structure it is unmistakable that the water molecules occupy similar sites, despite the introduced modification (Figure 4).Figure 4.

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.

Show MeSH
Related in: MedlinePlus