Recently, Presta and Rose proposed that a necessary condition for helix formation is the presence of residues at the N- and C-termini (called NTBs and CTBs) whose side chains can form hydrogen bonds with the initial four amides and the last four carbonyls of the helix, which otherwise lack intrahelical hydrogen bonding partners. We have tested this hypothesis by conformational analysis by circular dichroism (CD) of a synthetic peptide corresponding to a region (171-188) of the protein carboxypeptidase A; in the protein, residues 174 to 186 are helical and are flanked by NTBs and CTBs. Since helix formation in this peptide may also be stabilized by electrostatic interactions, we have compared the helical content of the native peptide with that of several modified peptides designed to enable dissection of different contributions to helix stability. As expected, helix dipole interactions appear to contribute substantially, but we conclude that hydrogen bonding interactions as proposed by Presta and Rose also stabilize helix formation. To assist in comparison of different peptides, we have introduced two concentration-independent CD parameters which are sensitive probes of helix formation.

Details of the stereochemistry of the 2'5' and 3'5' dinucleoside monophosphates of polynucleotides have been delineated in aqueous solution using nuclear magnetic resonance spectroscopy. Incorporation of these experimentally determined geometries into the structure of polynucleotides reveals that the intrinsic spatial configurations of the 2'5' bonds cannot support helical structures whereas the geometries of 3'5' bonds allow the formation of helical configurations for RNA.

The detailed conformational features and dynamics of the naturally occurring deoxyribotrinucleoside diphosphates d-TpTpT and d-TpTpC have been investigated at 20 degrees C and 80 degrees C in aqueous solution by nuclear magnetic resonance spectroscopy. The observed NMR parameters indicate that the conformational properties of the trimers are very similar to those of the constituent dimers and monomers, i.e., the monomers and dimers conserve their intrinsic conformational features when they become incorporated into oligomers. Model building indicate that the distant shieldings can originate from spatial configurations in which the central nucleotidyl unit is bulged out and the w'1w1, w'2w2 occupy /g+g+, g+g+/ domains.

Arguments are presented which show that conformations II and III proposed by Lee and Tinoco [Lee, C.H., and Tinoco, I., Jr. (1977), Biochemistry 16, 5403] for ribodinucleoside monophosphates in aqueous solution are untenable. It has been shown that ribodinucleoside monophosphates exist in aqueous solution as an equilibrium blend of the classically recognized right-handed stack (g-g-), loop stack (g+g+), skewed (g+t), and extended arrays. In order to determine the effect of epsilonA base on the conformer distribution in the equilibrium blend, detailed ring-current calculations were performed and the isoshielding curves for epsilonA were derived. Use of these curves vis-a-vis dimerization shift data indicates that introduction of epsilonA perturbs the equilibrium blend which causes an increase in the population of skewed (g+t) arrays.