STRUCTURAL POLYMORPHISM AND RAMAN CONFORMATION MARKERS OF CYCLIC DEOXYTRIADENYLIC ACID

X-ray analysis of two different trigonal crystal forms (space groups R 32 and P3) of cyclic deoxytriadenylic acid [c(dAp)(3)] indicates for e ach an asymmetric unit consisting of two conformationally similar c(dA p)3 molecules, Raman spectroscopy supports the X-ray interpretation fo r the R32 crystal, but identifies another c(dAp)(3) conformation not r evealed in the P3 X-ray structure. The results for the P3 crystal can be explained if an additional c(dAp)(3) conformer is present but not s ufficiently ordered within the lattice to contribute to X-ray diffract ion, The Raman signature of aqueous c(dAp)(3), which differs from sign atures of both the R32 and P3 crystals, exhibits backbone markers simi lar to those of thermally denatured DNA and indicates that c(dAp)(3) m olecules in solution populate a wider range of phosphoester ring confo rmations than in R32 and P3 crystals. Thus, polymorphism is observed f or both crystal and solution structures of c(dAp)(3). The results impl y a highly flexible phosphoester ring that may be relevant to the func tion of cyclic oligonucleotides as biological effecters. A novel Raman marker at 821 cm(-1) is demonstrated as diagnostic of phosphoester to rsions alpha and zeta in the gauche(+) range. Specific Raman markers a re also identified for the S-type (C2'-endo) deoxyadenosine conformati ons that occur in R32 and P3 crystal structures of c(dAp)(3).