Effect of a single 3'-methylene phosphonate linkage on the conformation of an A-DNA octamer double helix.
The three-dimensional structure of the self-complementary DNA octamer d(GCCCGpGGC) has been determined in the crystalline state using X-ray diffraction data to a nominal resolutoin of 2.12 measured from a very small crystal at DESY, Hamburg. The structure was refined with stereochemical restraints to an R value of 17.1%. d(GCCCGpGGC), containing one single 3'-methylene phosphonate linkage (denoted p), forms an A-DNA double helix with strict dyad symmetry, that is distinct from canonical A-DNA by a wide open major groove and a small average base-pair inclination against the helix axis. The conformation of the unmodified control d(GCCCGGGC) is known from an X-ray analysis of isomorphous crystals (Heinemann et al. (1987) Nucleic Acids Res. 15, 9531-9550). Comparison of the two structures reveals only minor conformational differences, most notably in the pucker of the reduced deoxyribose. It is suggested that oligonucleotides with charged 3'-methylene phosphonate groups may form stable duplexes with complementary DNA or RNA strands rendering them candidates for use as gene-regulatory antisense probes.
Heinemann
U
U
Abteilung Saenger, Freie Universität Berlin, FRG.
Rudolph
L N
LN
Alings
C
C
Morr
M
M
Heikens
W
W
Frank
R
R
Blöcker
H
H
D003461:Crystallography; D004247:DNA / Q000737:chemistry / Q000648:ultrastructure*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry; D063065:Organophosphonates; D013329:Structure-Activity Relationship; D014867:Water
D009841:Oligonucleotides; D063065:Organophosphonates; D014867:Water; D004247:DNA