Conformational analysis of brominated pA2'-5'A2'-5'A analogs. An NMR and model-building study.
NMR and model-building studies were carried out on pA2'-5'A2'-5'A and analogs in which one or more of the A residues were replaced by 8-bromoadenosine. Chemical shifts, coupling constants and NOE data were used to obtain structural information. The N/S equilibrium constant of the ribose rings as well as the phase angles and puckering amplitudes were determined from the experimental coupling constants with the aid of an improved version of the PSEUROT program. Chemical shifts in combination with NOE data were used to monitor base-base interactions and the orientation of the bases (syn or anti). The combined data suggest that different types of stacking interactions are present in the various compounds. Bromination of the first or second residue in the trimers results in a preference for N-type sugar and syn orientation of the base in these residues. When A(3) is brominated, an S-type sugar conformation together with a syn orientation of the base is favoured at the 2' terminus. Energy-minimized models of the different stacking interactions are presented which fit the present collection of data. The possible correlation between biological activity of these compounds and their conformation is briefly discussed.
van den Hoogen
Y T
YT
Gorlaeus Laboratories, Leiden University, The Netherlands.
Hilgersom
C M
CM
Brozda
D
D
Lesiak
K
K
Torrence
P F
PF
Altona
C
C
D000241:Adenosine / Q000031:analogs & derivatives* / Q000032:analysis; D001665:Binding Sites; D055598:Chemical Phenomena; D002621:Chemistry; D004735:Energy Transfer; D009682:Magnetic Resonance Spectroscopy; D008962:Models, Theoretical; D008968:Molecular Conformation; D009841:Oligonucleotides; D013696:Temperature
D009841:Oligonucleotides; C036038:8-bromoadenosine; D000241:Adenosine