Binding thymine

Fig. 21. (a) Diagrammatical representation of an allosteric receptor mechanism (b) allosteric binding of a thymine derivative promoted on uptake (34). 

Like Thr 124 and Thr 215, the Asn 69 and Asn 159 residues occupy equivalent positions in the two homologous motifs of TBP. By analogy with the symmetric binding of a dimeric repressor molecule to a palindromic sequence described in Chapter 8, the two motifs of TBP form symmetric sequence-specific hydrogen bonds to the quasi-palindromic DNA sequence at the center of the TATA box. The consensus TATA-box sequence has an A-T base pair at position 4, but either a T-A or an A-T base pair at the symmetry-related position 5, and the sequence is, therefore, not strictly palindromic. However, the hydrogen bonds in the minor groove can be formed equally well to an A-T base pair or to a T-A base pair, because 02 of thymine and N3 of adenine occupy nearly stereochemically equivalent positions, and it is sufficient, therefore, for the consensus sequence of the TATA box to be quasi-palindromic. 

Cherny D.Y., Belotserkovskii B.P., Frank-Kamenetskii M.D., Egholm M., Buchardt O., Berg R. H., Nielsen, P.E. DNA unwinding upon strand-displacement binding of a thymine-substituted polyamide to double-stranded DNA. Proc. Natl Acad. Sci. USA 1993 90 1667-1670... 

Hoechst 33342 [2 -(4-ethoxyphenyl)-5-(4-methyl-l-piperazinyl)-2,5 -bi-IH-benzimidazole Ho342 I], a bisbenzimidazole dye, binds to adenine/thymine-rich regions in the minor groove of DNA. This dye induces apoptosis and inhibits topo 1 activity in vivo. It has been suggested that the destruction of immunoreactive topo I and topo I-DNA complexes or cleavable complexes results in inhibition of topo I activity, a key step in the Hoechst 33342-induced apoptotic process [40]. 

Figure 2 Double-stranded oligonucleotide photoprobes that simulate modified DNA and intended to cross-link to DNA-binding proteins. (A) Probe modeling interstrand cross-linking by cisplatin Source From Ref. [63], with permission from the American Chemical Society via the Rightslink service (license number 2458870278307 granted June 30, 2010). The benzophenone probe prior to reaction with DNA is shown in the lower part of the panel. (B) Photoaffinity probe for bacterial DNA repair proteins. TT is a simulated thymine dimer intended to be recognized as a site of damage in DNA, and T (two instances) is the diazirine thymine derivative T Source From Ref. [64], with permission from Wiley.

Table XIX contains stability constants for complexes of Ca2+ and of several other M2+ ions with a selection of phosphonate and nucleotide ligands (681,687-695). There is considerably more published information, especially on ATP (and, to a lesser extent, ADP and AMP) complexes at various pHs, ionic strengths, and temperatures (229,696,697), and on phosphonates (688) and bisphosphonates (688,698). The metal-ion binding properties of cytidine have been considered in detail in relation to stability constant determinations for its Ca2+ complex and complexes of seven other M2+ cations (232), and for ternary M21 -cytidine-amino acid and -oxalate complexes (699). Stability constant data for Ca2+ complexes of the nucleosides cytidine and uridine, the nucleoside bases adenine, cytosine, uracil, and thymine, and the 5 -monophosphates of adenosine, cytidine, thymidine, and uridine, have been listed along with values for analogous complexes of a wide range of other metal ions (700). Unfortunately comparisons are sometimes precluded by significant differences in experimental conditions.

Platination of the N3 position in 1-substituted uracil and thymine derivatives requires proton abstraction and usually occurs only at high pH, but the Pt-N3 bond, once formed, is thermodynamically stable (log K 9.6) [7]. Platinum binding to N3 increases the basicity of 04, which becomes an additional binding site leading to di- and trinuclear complexes. A list of X-ray structurally characterized species is given by Lippert [7]. Pt complexes of uracil and thymine can form intensely colored adducts (e.g. platinum pyrimidine blues), which show anticar-cinogenic activity analogously to the monomeric species [7]. 

Hg2 + selectively binds the AT region, apparently due to its great affinity for thymine. Thus, Hg2+ interacts with DNA at nitrogen atoms, replacing hydrogen between the thymine and adenine bases [114]. This interaction results in increased helix stability and an increased diameter of the double helix, approximating the difference between the atomic radius of hydrogen and mercury [116]. 

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