Minor groove functional groups are critical for the B-form conformation of duplex DNA.
Two analogue bases are described: 3-deazaadenine is a derivative of adenine from which N3 has been deleted and 3-methyl-2-pyridone is a C-nucleoside that mimics thymine but lacks the O2 carbonyl. The dc(3)A-dm(3)2P base pair is similar to dA-dT but eliminates the polar functional groups in the minor groove. The presence of this base pair in dA-dT rich sequences results in destabilized duplexes or conformational preferences for monomolecular hairpins rather than bimolecular duplexes. When present in dG-dC rich sequences, no significant differences in helix stability are observed. These differences are explained on the basis of hydration effects, most notably, the elimination of the minor groove spine of hydration normally present in dA-dT rich sequences. CD spectra suggest that sequences with a fully modified core (four analogue base pairs) are more A-like helices than B-like helices. Sequences containing two analogue base pairs can be transformed to A-like helices under conditions of high salt, or 65% trifluoroethanol. These conformational changes are also explained in terms of a loss of hydration in the minor groove that normally stabilizes the B-form conformation. In the absence of such hydration, the helices are conformationally mobile and adopt a more A-like helix form.
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Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02167, USA.
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D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D006813:Humidity; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry*; D009841:Oligonucleotides / Q000737:chemistry; D011067:Poly dA-dT / Q000737:chemistry; D011728:Pyridones / Q000737:chemistry; D012492:Salts / Q000737:chemistry; D012965:Sodium Chloride / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D013873:Thionucleotides / Q000737:chemistry; D014270:Trifluoroethanol / Q000737:chemistry
D009692:Nucleic Acid Heteroduplexes; D009841:Oligonucleotides; D011728:Pyridones; D012492:Salts; D013873:Thionucleotides; D011067:Poly dA-dT; D012965:Sodium Chloride; C055133:3-deazaadenine; D014270:Trifluoroethanol; D004247:DNA; D000225:Adenine