Guanine terms Links

In addition to its influence on protein—protein interactions, phosphorylation also affects protein structure and activity. One case involves a protein termed dematin headpiece (DHP), an actin-binding protein found in a variety of tissues including heart, brain, skeletal muscle, kidney, and lung." DHP is known to interact with Ras-guanine nucleotide exchange factor (Ras-GRF2) and this interaction can modulate MARK pathways, which can link the cytoskeleton and signaling pathways." ... 

In general terms, both steric effects and electronic factors are expected to play a role in determinating the reactivity of square-planar platinum complexes. The presence of planar amine ligands in cis- or /ran.y-Pt(anion )2 complexes and their orientation with respect to the coordination plane, as well as their substituents, can reduce the rates of DNA binding or thio binding compared to aliphatic ammine and amine complexes. Especially, substituents close to the coordination site should be expected to slow down axial substitution reactions at Pt. As there is now little doubt that DNA platina-tion is a key event (or THE key event) in the mechanism of action of platinum anticancer drugs, attention to the process of formation of the major adduct (GG) as an intrastrand cross-link between N(7) atoms of two adjacent guanine (G) residues, will remain important. 

An intrastrand cross-link formed by cisplatin and adjacent guanine residues causes an unusally distorted base pair (bp) step, known as the Lippard bp step. A study of the effects of neighbouring nucleotides to the cross-linked G G has shown that the 3 -nucleotide has little effect, but the 5 -nucleotide has a dramatic effect. The 5 residue always maintains an S pucker, but the canting varies, depending on the substituent. Bleomycin causes two major lesions to DNA, formation of a 4 -keto abasic site and strand cleavage to yield a 3 -phosphog-lycolate and a 5 -phosphate. As a model for the 4 -keto abasic site, an NMR structure of a 13-mer DNA duplex containing an abasic site has been reported." It was found that for both the a- and p-anomers, the abasic site was extrahelical, and that the duplex showed very little distortion to the backbone. This was discussed in terms of repair of such lesions in vivo. 

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