ABSTRACT
In recent years various examples of highly stable two-residue hairpin loops (miniloops) in DNA have been encountered. As the detailed structure and stability of miniloops appear to be determined not only by the nature and sequence of the two bases in the loop, but also by the closing base pair, it is desirable to carry out in-depth studies of especially designed small model DNA compounds. Therefore, a circular DNA dumbbell-like molecule is tailored to consist of a stem of three Watson-Crick base pairs, flanked on each side by a minihairpin loop. The resulting circular DNA decamer 5'-d
Subject(s)
DNA, Circular/chemistry , Nucleic Acid Conformation , Base Sequence , Kinetics , Molecular Sequence Data , ThermodynamicsABSTRACT
The conformational behavior of DNA minihairpin loops is sensitive to the directionality of the base pair that closes the loop. Especially tailored circular dumbbells, consisting of a stem of three Watson-Crick base pairs capped on each side with a minihairpin loop, serve as excellent model compounds by means of which deeper insight is gained into the relative stability and melting properties of hairpin loops that differ only in directionality of the closing pair: C-G vs G-C. For this reason the thermodynamic properties of the circular DNA decamers 5'-d
Subject(s)
DNA, Circular/chemistry , Nucleic Acid Conformation , Base Sequence , Chemical Phenomena , Chemistry, Physical , Molecular Sequence Data , ThermodynamicsABSTRACT
The circular DNA decamer 5'-d
Subject(s)
DNA, Circular/chemistry , Magnetic Resonance Spectroscopy , Models, Molecular , Nucleic Acid Conformation , ProtonsABSTRACT
A one- and two-dimensional NMR study has been performed on seven A(2'-5')A(2'-5')A fragments containing 9-(3'-fluoro-3'-deoxy-beta-D-xylofuranosyl)-adenine (AF) or 3'-fluoro-3'-deoxyadenosine (AF) residues at different positions, and on the corresponding monomers. A(2'-5')A(2'-5')A served as a reference compound. The fluoro substituent governs the conformation of the sugar ring: an AF residue displays mainly N-type sugar and the ring is considerably flattened (phi N approximately 30 degrees) compared to AF residues (phi S approximately 40 degrees), which exhibit almost pure S-type conformation. Moreover, in AF moieties the rotamer distribution around torsion angle gamma (O5'-C5'-C4'-C3') and the base orientation are influenced to a large extent by the presence of the fluorine substituent. The sugar rings of nonfluorinated residues in the trimers appear rather flexible. A possible correlation between the conformational characteristics of the fluorinated fragments and their biological activity has been found: the fragments that meet the prerequisites for binding to RNase L indeed show enhanced binding to this endonuclease. Furthermore, substitution of the 3'-OH group of the second residue by hydrogen or of the 3'-OH group of the 2'-terminal residue by fluorine or hydrogen results in increased resistance towards 2'-5'-phosphodiesterase.
Subject(s)
Adenine Nucleotides/chemistry , Deoxyadenosines/chemistry , Endoribonucleases/metabolism , Adenine Nucleotides/pharmacology , Deoxyadenosines/pharmacology , Magnetic Resonance Spectroscopy , Molecular Conformation , Polymers , Structure-Activity RelationshipABSTRACT
The naturally occurring RNA-nucleopeptide H-Ala-Tyr[5'-pUUAAAAC-3']-NH2 is prepared via a solid-phase phosphite triester approach using N-SiOMB/O-TBDMS-protected nucleosides. Preliminary 1H-NMR studies show that the peptidyl unit has a remarkable effect on the conformational behaviour of the RNA moiety in the nucleopeptide.
Subject(s)
Oligoribonucleotides/chemistry , Peptide Fragments/chemical synthesis , Poliovirus/chemistry , RNA, Viral/chemistry , Ribonucleoproteins/chemical synthesis , Viral Proteins/chemical synthesis , Magnetic Resonance Spectroscopy , Nucleic Acid Conformation , Nucleoproteins/chemistry , Peptide Fragments/chemistry , Ribonucleoproteins/chemistry , Viral Proteins/chemistryABSTRACT
The circular DNA decamer 5'-d [formula: see text] 3' is studied in solution by means of NMR spectroscopy. At low temperature the molecule adopts a dumbbell structure with three Watson-Crick C-G base pairs and two two-residue loops in opposite parts of the molecule. On raising the temperature another conformer appears, in which the closing C-G base pair in the 5'-GTTC-3' loop is disrupted, whereas the opposite 5'-CTTG-3' loop remains stable. The two conformers are in slow equilibrium over a limited temperature range.