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Handed Coiled DNA

Selective Binding of Drug Enantiomers to Left- and Right-Handed Coiled DNA [Pg.211]

Would you like left- or right-handed DNA with your drug  [Pg.211]

Enantiomeric forms of daunorubicin bind with DNA and cause it to coil with opposite handedness. [Graphic courtesy John O. Trent, Brown Cancer Center, Department of Medicine, University of Louisville, KY. Based on work from Qu, X. Trent, J.O., Fokt, I., Priebe, W., and Chaires, J.B., Allosteric, Chiral-Selective Drug Building to DNA, Proc. Natl. Acad. Sci. U.S.A., 2000 (Oct. 24) 97(22), 12032-12037.] [Pg.211]

12 Molecules with More than One Chirality Center [Pg.211]

So far we have mainly considered chiral molecules that contain only one chirality center. Many organic molecules, especially those important in biology, contain more than one chirality center. Cholesterol (Section 23.4B), for example, contains eight chirality centers. (Can you locate them ) We can begin, however, with simpler molecules. Let us consider 2,3-dibromopentane, shown here in a two-dimensional bond-line formula. 2,3-Dibromopentane has two chirality centers  [Pg.211]


THE CHEMISTRY OF... Selective Binding of Drug Enantiomers to Left- and Right-Handed Coiled DNA 217... [Pg.10]

Local variations in the sequence of nucleotides affect the conformation of a DNA molecule and it is clear that the helix is not uniformly coiled throughout the entire length.80 103,124 129 134 While most helix segments probably have a right-handed twist others may be left-handed. Most DNA is probably in the B form but there are segments in the A form. These may arise from formation of hybrid duplexes with RNA, which assume the A conformation and are also favored by certain base sequences. Rules for predicting the DNA conformation from the nucleotide sequence have been proposed.116135 In the simplest case135 we consider each pair of adjacent nucleotides in the double helix. [Pg.216]

The nucleosome consists of a 200-base-pair (bp) DNA strand making two left-handed coils around an octamer of histone proteins consisting of two copies each of histones H2A, H2B, H3, and H4, and a single copy of the histone HI (Fig. 6.3). [Pg.195]

Fig. 6.3. A DNA thread making two left-handed coils around each of a series of protein spools. A single spool consists of an octamer of histone proteins, two each of H2A, H2B, H3, and H4. The ninth histone protein, H1, may be located in the linker region between spools immediately adjacent to the spool. The DNA and histones make up the nucleosome. (From Calladine CR, Drew HR. Understanding DNA The Molecule and How It Works, 2nd Ed. New York Academic Press, 1997 with permission.)... Fig. 6.3. A DNA thread making two left-handed coils around each of a series of protein spools. A single spool consists of an octamer of histone proteins, two each of H2A, H2B, H3, and H4. The ninth histone protein, H1, may be located in the linker region between spools immediately adjacent to the spool. The DNA and histones make up the nucleosome. (From Calladine CR, Drew HR. Understanding DNA The Molecule and How It Works, 2nd Ed. New York Academic Press, 1997 with permission.)...
When two nucleic acid strands have complementary nucleic acid sequence, they can undergo hybridization to form double-stranded duplex structures. DNA forms a double-stranded helix composed of two complementary helical polynucleotide chains, aligned antiparallel, which are coiled around a common axis. In helix form, the anionic backbone lies on the outside of the structure with the nucleobases in the core, perpendicular to the axis and separated by a distance of 3.4 A. This B-form helix (Figure 2a) has a right-handed coil that repeats itself every 34 A with a turn every... [Pg.3188]

The capability to elongate nucleotide chains necessitates the exposure of template nucleotide sequences. Therefore the polymerase activity must be preceded by the continuous unwinding of the DNA duplex. The circular chromosome of E. coli exists as a left-handed supercoil (Section 7.3). Initially, the left-handed coils counterbalance the right-handed twists generated by the advancement of the replication fork. However, after approximately 5% of the DNA has been replicat, right-handed supercoils may be produced and replication would cease because movement of the fork is impaired. [Pg.225]

In the chromatin of eukaryotic cells DNA forms a coiled-coil structure with an approximately equal weight of a mixture of five basic proteins known as histones. Four of these histones in pairs form an octa-mer around which the DNA duplex occurs in a left-handed helix. The DNA octamer complex is called a nucleosome. Each nucleosome contains about 140 base pairs of DNA in a nuclease-resistant nucleosome core and approximately 60 base pairs of spacer between core particles. Histone HI binds to the chromatin independently of the octamer and is the first histone to dissociate from the chromatin when the ionic strength is raised. Beyond the nucleosome the higher order structure of the chromosome involves coiled-coil structures with varying degrees of regularity. [Pg.646]

Manipulation of DNA in such a precise manner demonstrates what can be achieved when the nature of nanoscale interactions is well understood and can be controlled. As more and more becomes known about similar molecular recognition motifs in the natural world the potential to use other biomaterials as structural components will increase. Other structural biomolecules that could be targets for unnatural manipulation include collagen [8] and clathrin proteins [9], shown in Fig. 8.2. The former is a polypeptide that forms a triple helical coil in which the individual strands are left handed but the resulting supercoil is right handed. It provides structure to bone and cartilage and has many other rigidifying functions. [Pg.234]

The hydrodynamic properties of solutions of native double-stranded DNA have thus far eluded complete quantitative interpretation, in spite of very extensive investigation. A synthesis of experimental data has recently been furnished by Doty [84 ) some of the earlier experimental results may be found in the papers of Doty, Bunce-McGiix, and Rice (86) Doty, Makmur, Eignek, and Schildkraut (55) and Kawade and Watanabe (135 ). It is easy to see that the double helices are not perfectly inflexible, for the observed intrinsic viscosities are far lower than those of rigid rods or ellipsoids with the Watson-Crick dimensions, p = Af/4600. On the other hand, the customary flexible-coil treatments also do not apply to these data. For example, if the correlation plot of against g (a) M l [) ], / is attempted, it is found that... [Pg.274]


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