PDBsum entry 1k1h

DNA

PDB id: 1k1h

Contents

DNA/RNA

PDB id:

1k1h

Name:

DNA

Title:

Heteroduplex of chirally pure methylphosphonate/DNA duplex

Structure:

5'-d( Tp Gp Tp Tp Tp Gp Gp C)-3'. Chain: a. Engineered: yes. 5'-d( Cp (Cmr)p (Rmp)p (Rmp)p (Smp)p (Cmr)p (Rmp))-3'. Chain: b. Engineered: yes

Source:

Synthetic: yes. Synthetic: yes

NMR struc:

1 models

Authors:

V.Thiviyanathan,K.V.Vyazovkina,E.K.Gozansky,E.Bichenchova, T.V.Abramova,B.A.Luxon,A.V.Lebedev,D.G.Gorenstein

Key ref:

V.Thiviyanathan et al. (2002). Structure of hybrid backbone methylphosphonate DNA heteroduplexes: effect of R and S stereochemistry. Biochemistry, 41, 827-838. PubMed id: 11790104 DOI: 10.1021/bi011551k

Date:

25-Sep-01 Release date: 19-Jun-02

DNA/RNA chains

T-G-T-T-T-G-G-C 8 bases

C-CMR-RMP-RMP-SMP-CMR-RMP 7 bases

DOI no: 10.1021/bi011551k

Biochemistry 41:827-838 (2002)

PubMed id: 11790104

Structure of hybrid backbone methylphosphonate DNA heteroduplexes: effect of R and S stereochemistry.

V.Thiviyanathan, K.V.Vyazovkina, E.K.Gozansky, E.Bichenchova, T.V.Abramova, B.A.Luxon, A.V.Lebedev, D.G.Gorenstein.

ABSTRACT

Methyl phosphonate oligonucleotides have been used as antisense and antigene agents. Substitution of a methyl group for oxygen in the phosphate ester backbone introduces a new chiral center. Significant differences in physical properties and hybridization abilities are observed between the R(p) and S(p) diastereomers. Chirally pure methylphosphonate deoxyribooligonucleotides were synthesized, and the solution structures of duplexes formed between a single strand heptanucleotide methylphosphonate, d(Cp(Me)Cp(Me)Ap(Me)Ap(Me)Ap(Me)Cp(Me)A), hybridized to a complementary octanucleotide, d(TpGpTpTpTpGpGpC), were studied by NMR spectroscopy. Stereochemistry at the methylphosphonate center for the heptanucleotide was either RpRpRpRpRpRp (R(p) stereoisomer) or RpRpRpSpRpRp (S(p) stereoisomer, although only one of the six methylphosphonate centers has the S(p) stereochemistry). The results show that the methylphosphonate strands in the heteroduplexes exhibit increased dynamics relative to the DNA strand. Substitution of one chiral center from R(p) to S(p) has a profound effect on the hybridization ability of the methylphosphonate strand. Sugars in the phosphodiester strand exhibit C(2)(') endo sugar puckering while the sugars in the methyl phosphonate strand exhibit an intermediate C(4)(') endo puckering. Bases are well stacked on each other throughout the duplex. The hybridization of the methylphosphonate strand does not perturb the structure of the complementary DNA strand in the hetero duplexes. The sugar residue 5' to the S(p) chiral center shows A-form sugar puckering, with a C(3)(')-endo conformation. Minor groove width in the R(p) stereoisomer is considerably wider, particularly at the R(p) vs S(p) site and is attributed to either steric interactions across the minor groove or poorer metal ion coordination within the minor groove.