STRUCTURE AND STABILITY OF CYTOSINE DEOXYOLIGONUCLEOTIDES MULTIPLEXES

It has very recently been reported that deoxyribonucleic acid oligomer s of cytosine with sequences such as d-T(C-N) T aggregate into tetrast randed structures [J. L. Leroy et al. (1993), Biochemistry, Vol. 32, p p. 6019-6031; K. Gehring et al. (1993), Nature, Vol. 363, pp. 561-565; S. Ahmed (1994), Structural Biology, Vol. 1, pp. 83-88]. Using gel fi ltration chromatography we have followed that the oligomer dC(10) aggr egates into a mixture of duplex, tetraplex, and octaplex structures. W e have also found that at the concentration used for Raman spectroscop y (0.05 M in base residues), these structures remain stable from pH 5 to pH 8 at 5 degrees C. The Raman spectra of these oligomers in a 0.1 M NaCl solution at pH 7 and 5 degrees C show a remarkable resemblance to the Raman spectra of the A-form double-helical ribonucleic acid pol ymer of cytosine taken at pH 5.5 and room temperature [C. H. Chen and G. J. Thomas, Jr. (1977), Biopolymers, Vol. 16, pp. 765-789]. This app ears to be the first time that this A-type furanose ring pucker has be en reported in deoxyoligonucleotides in aqueous solution at low salt a nd pH 5.5-7. The gel filtration chromatography and the uv melting beha vior of the annealed dC(10) solutions show the presence of an equilibr ium mixture of multiplexes with multiple melting transitions. Very slo w annealing of dC(10) solutions in the pH range 6.5-7.0 also produced a similar equilibrium mixture of multiplexes, but at a much slower rat e. Rapidly cooled samples tended to change to the equilibrium mixture over a period of several days. (C) 1997 John Wiley & Sons, Inc.