Loop conformation, double

Compounds with cis double bonds in the side chain were in general found to be more potent and efficacious than their triple-bond congeners, both in in vivo and in in vitro functional assays [98, 106, 107]. QSAR models have been generated for the compounds with unsaturated [108] and l, l -dimethyl [96] side chains to determine more precisely the pharmacophoric requirements of the receptor. It is postulated that for optimum potency, the side chain must be of a suitable length and flexibility to have the ability to loop back so that its terminus is in proximity to the phenolic ring. The widely used, potency enhancing 1 - and 2 -methyl substituents would be expected to increase the tendency of the side chain to adopt a looped back, rather than an extended conformation. 

The Watson and Crick model for DNA as a double helix is only a generalized model to describe much more complex structures. Along with the typical double helix there exist structural elements such as supercoils, kinks, cruciforms, bends, loops, and triple strands as well as major and minor grooves. Each of these structural elements can vary in length, shape, location, and frequency. Even the simple DNA double helix can vary in pitch (number of bases per helical turn), sugar pucker conformation, and helical sense (whether the helix is left-or right-handed). 

The optical results at low salt concentration have been interpreted in terms of the presence of the two conformations given by reactions (16.24) and (16.25). The latter structure is only partially double-stranded and incorporates the hairpin loop region in which four bases are not paired. The lower transition temperature, which is concentration-dependent, with the larger melting enthalpy is ascribed to the disruption of the full duplex structure, which is a bimolecular process. The higher temperature transition (with a lower transition enthalpy) is attributed to the disruption of the hairpin structure, which is a... 

Final proof for the inferred structure (1) for cyclosporin A and a first insight in the shape of the molecule resulted from X-ray analysis and high-resolution NMR spectra. The preparation of a crystallized derivative containing a heavy atom was achieved by an addition reaction using iodine and thallium(I) acetate. Instead of the expected iodoacetoxy derivative, the cyclic product (11) was obtained. Obviously, the reaction proceeded by a selective addition of iodine to the double bond of the MeBmt unit followed by an internal cyclization with the participation of the OH group. Iodocyclosporin A (11) reverted easily with Zn powder in acetic acid into genuine cyclosporin A by rranr-elimination. X-ray analysis [6] revealed that iodocyclosporin A assumes a rather rigid backbone conformation. The amino acids 1-6 adopt an antiparallel, markedly twisted /i-pleated sheet conformation, whereas the residues 7-11 form a loop. 

While RNA molecules usually exist as single chains, they often form hairpin loops consisting of double helices in the A conformation (Moore, 1999). The best-known forms of RNA are the low-molecular-weight tRNA molecules. In all of them the bases can be paired to form a cloverleaf structure with three hairpin loops and sometimes a fourth. The cloverleaf structure of tRNA is further folded into an T-shape conformation with the anticodon triplet and the aminoacyl attachment CCA forming the two ends. 

Similar to what we demonstrated for the non-methylated sequences we investigated the methylated sequences in the context of single or double nucleotide replacements. For all replacements tested we observed the occurrence of a single conformer comprising the m2GGm62Am62A loop. 

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