Cytosine VOLUME

NMR solution structures of two cisplatin-DNA decamers containing interstrand cross-links demonstrated that this minor adduct also has characteristic structural features [13] [14]. In particular, the platinum atom lies in the minor groove, the complementary cytosines are extrahelical, and there is a switch in the double helix to a left-handed form localized at the site of the adduct. These distortions bend the helix axis towards the minor groove by approximately 20°-40° and unwind the duplex by 76°-80°. More detailed descriptions of Pt-DNA complexes may be found in other chapters in this volume. 

Fig. 2. Schematic of track of an Argon ion-beam in DNA. A high-energy density core is generated by deposition of ca. 50% of the energy of the ion in a relatively small volume. At 77 K, neutral sugar radicals are stabilized largely in the core. A much larger region of space formed by delta rays from the core is characterized by low LET-like spurs. Ion base radicals are stabilized in the spurs, with one-electron-reduced cytosine actually existing as a protonated species.

DNA has a form of double helix and contains nearly 3 billion base pairs, each of which consists of one of four types of nucleotides such as adenine, thymine, cytosine, and guanine. The human genome, the complete human DNA, would be equivalent to about 250 volumes of Manhattan phone directories when it is printed. Figure B.l illustrates the processes associated with protein synthesis transcription, translation, posttranslation modification (PTM), and folding. 

Compounds with different lipid solubility have different fates in tissue. This is most clearly demonstrated in the brain using ventriculocisternal perfusion [88]. In these experiments, solutes delivered into the cerebrospinal fluid permeate through the ependyma into the extracellular space of the brain. Three classes of compounds, with different patterns of local distribution, have been identified (a) water-soluble compounds that remain in the extracellular space of the brain, occupying a volume fraction of 15-20% (e.g., sucrose and EDTA), (b) large, lipid-soluble compounds that have slow capillary transport, but quickly enter the cells of the brain, occupying a volume fraction of 50-200% (e.g., mannitol, creatinine, cytosine arabinoside), and (c) small, lipid-soluble compounds that are rapidly removed from the brain by capillary transport (e.g., H2O, ethanol, l,3-bis(2-chloroethyl)-l-nitrosourea (BCNU). Similar behavior probably occurs in extracranial tissues as well. 

To date, only two applications of complete relaxation matrix derived distance restraints have been reported for RNA. MARDIGRAS provided "precise" distance restraints for the structure determination of a 17mer RNA with a flexible loop (26) and a 31mer hairpin with a large internal loop (18). For the latter, assignments and NOE volume extraction was made feasible through deuteration of all cytosines. 

Figure 1. Hydropathy-Molar Volume plot demonstrating the correlation between two physico-chemical properties1 of amino acid residues (single letter code) and their codon sequences. Amino acid residues having codons with adenine in the middle position (A/AA/) are typically hydrophilic and moderate in size, those with NTN codons are typically hydrophobic and moderate in size, and those with A/CA/ codons are typically average in hydropathy while small in size. Amino acid residues having NGN codons show no obvious grouping in hydropathy-molar volume space. Because serine uses codons bearing either cytosine or guanine in the second position, this residue is in a unique position.

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