Conformational furanose rings

The furanose rings of the deoxyribose units of DNA are conformationally labile. All flexible forms of cyclopentane and related rings are of nearly constant strain and pseudorotations take place by a fast wave-like motion around the ring The flexibility of the furanose rings (M, Levitt, 1978) is presumably responsible for the partial unraveling of the DNA double helix in biological processes. 

Notice that the eclipsed conformation of d ribose derived directly from the Fischer pro jection does not have its C 4 hydroxyl group properly oriented for furanose ring forma tion We must redraw it m a conformation that permits the five membered cyclic hemi acetal to form This is accomplished by rotation about the C(3)—C(4) bond taking care that the configuration at C 4 is not changed... 

Conformation of D ribose suitable for furanose ring formation... 

Figure 3 The underlying tree of a furanose ring in nucleic acids. Atoms are numbered 1,. . . , 5 corresponding to the natural tree ordering. All bond lengths are fixed. Arrows illustrate five internal coordinates that determine the ring conformation.

The practice of including the conformation after the name of the parent monosaccharide should be used only with caution because not all conformations are known with certainty. In the case of furanose rings especially, conformations might differ between the crystalline and solution states. 

Jh-3. f 20.2 Hz in D2O), concluded that the furanose ring adopts the envelope form with C-3 endo, which differs greatly from the conformation of... 

Deoxy-3-fluoro- -D-xylofuranosyl)cytosine (821) was prepared by condensation of 2,5-di-0-benzoyl-3-deoxy-3-fluoro-D-xylofuranosyl bromide with bis(trimethylsilyl)cytosine (773). It was proposed that 1 -(3 1eoxy-3-fluoro-)S-D-arabinofuranosyl)uracil (823), prepared from l-(2,3-anhy-dro-)S-D-lyxofuranosyl)uracil (822) with anhydrous HF ( 8% in 1,4-dioxane 116 °, 41 h, 3% yield), has a twist conformation of the furanose ring(°r, acetone- 4-D20 . Jn-vf 13.5, Hz). Reexamination ... 

The conformations of the furanose ring in 250 nucleoside and nucleotide structures were analysed by Bartenev et al. (1987). These authors made the assumption, referred to above, that intermolecular interactions have a random effect on the structure in the crystal, and that the probability JVg of a structure crystallizing in a non-ground-state conformation is the same as the probability of it arising in thermal equilibrium at ambient temperature T in solution (6). (A difficulty arises immediately with the definition of the temperature, because structural parameters for molecules in crystals are... 

Finally, the effect of neomycin-B flexibility on its enzymatic inactivation by Enterococcus faecalis APH(3 ) was tested. This enzyme catalyzes the transfer of a phosphate group from ATP to position 4 of ring I. In this case, the X-ray structure of the enzyme in complex with neomycin-B shows that the antibiotic structure recognized by the enzyme and the target RNA are remarkably similar (see Fig. 7) [40]. In fact, they mainly differ in the conformation adopted by the furanose ring of III (C3-endo and close to C2-endo for the RNA- and enzyme-bound conformations respectively). 

Monosaccharides have many structural variations that correspond to local minima that must be considered. Acyclic carbohydrates can rotate at each carbon, and each of the three staggered conformers is likely to correspond to a local minimum. The shapes of sugar rings also often vary. Furanose rings usually have two major local minima and a path of interconversion. Experimental evidence shows a clear preference for only one chair form for some pyranose rings, but others could exist in several conformers. For exanqple, the and conformers must all be considered as possible structures for L-iduronate, as discussed by Ragazzi et al. in this book. 

The conformational properties of furanose rings have received considerable attention in recent years because of the impact these properties may have in mediating biological processes . Most notable in this respect are the p-D-ribofuranose 1 and 2-deoxy-p-D-erythro-pentose 2 (Scheme 1) components of ribo- (RNA) and deoxyribonucleic (DNA) acids. It is well known that the furanose ring adopts specific shapes depending on its local structural environment in a biopolymer. For example, in tRNA, the... 

The conformational dynamics of furanose rings may be described by the mechanisms of pseudorotation and inversion. The former mechanism describes a continuous pathway of interconversion between twenty idealized non-planar (envelope, twist) conformers (Figures 1 and 2) that does not involve the planar form (e.g., - E4 — ... 

Energy profiles in Figure 14 also reveal that planar furanose forms are often of lower energy than puckered conformers. For example, relative conformational energies determined for 7 with the 3-21G basis set indicate that the planar conformer is more stable than the Eq conformer in 8, the planar conformer is calculated to be more stable than. These observations suggest that the conformational dynamics of some furanose rings may not be completely described by pseudorotation in these cases,conformer interconversion may occur by both inversion and pseudorotational pathways, with the latter being the more preferred route. 

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