Structure of a tethered cationic 3-aminopropyl chain incorporated into an oligodeoxynucleotide: evidence for 3'-orientation in the major groove accompanied by DNA bending.
The structure of the dodecamer d(CGCGAATXCGCG)(2), in which X = Z3dU, 5-(3-aminopropyl)-2'-deoxyuridine, was determined. At neutral pH, Z3dU introduced a positive charge into the major groove. NMR spectroscopy revealed that the Z3dU omega-aminopropyl moiety oriented in the 3'-direction from the site of modification. Watson-Crick base pairing remained intact throughout the dodecamer. The presence of the charged amino group in the major groove resulted in a 0.24 ppm upfield shift of one (31)P NMR resonance in the 3'-direction at the phosphodiester linkage between nucleotides C(9) and G(10). Molecular dynamics calculations restrained by distances obtained from (1)H NOE data and torsion angles obtained from (1)H NMR (3)J coupling data, and in which the omega-amino group was constrained to be proximate to G(10)O(6), predicted from the (31)P NMR data and molecular modeling (Dande, P.; Liang, G.; Chen, F.-X.; Roberts, C.; Nelson, M. G.; Hashimoto, H.; Switzer, C.; Gold, B. Biochemistry 1997, 36, 6024-6032), were consistent with experimental NOEs. These refined structures exhibited bending. The distance from the amino group to the 5'-phosphate oxygen of Z3dU was >5 A, which indicated that in this dodecamer the Z3dU amino group did not participate in a salt bridge to its 5'-phosphate.
Department of Chemistry and Center in Molecular Toxicology, Vanderbilt University, Nashville, Tennessee 37235, USA.
Zhijun
Z
Li
Li
L
Huang
Prasad
P
Dande
Barry
B
Gold
Michael P
MP
Stone
D004247:DNA / Q000737:chemistry*; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D055672:Static Electricity
D009841:Oligonucleotides; C053601:5-(3-aminopropyl)-2'-deoxyuridine; D004247:DNA; D003857:Deoxyuridine