Dinucleotide cross-links

This thiol-disulfide interconversion is a key part of numerous biological processes. WeTJ see in Chapter 26, for instance, that disulfide formation is involved in defining the structure and three-dimensional conformations of proteins, where disulfide "bridges" often form cross-links between q steine amino acid units in the protein chains. Disulfide formation is also involved in the process by which cells protect themselves from oxidative degradation. A cellular component called glutathione removes potentially harmful oxidants and is itself oxidized to glutathione disulfide in the process. Reduction back to the thiol requires the coenzyme flavin adenine dinucleotide (reduced), abbreviated FADH2. 

Baskin, L.S., and Yang, C.S. (1980a) Cross-linking studies of cytochrome P-450 and reduced nicotinamide adenine dinucleotide phosphate-cytochrome P-450 reductase. Biochemistry 19, 2260-2264. 

Mitomycin (mitomycin C, Mitocin-C, Mutamycin) is an antibiotic that is derived from a species of Streptomyces. It is sometimes classified as an alkylating agent because it can covalently bind to and cross-link DNA. Mitomycin is thought to inhibit DNA synthesis through its abihty to alkylate double-strand DNA and bring about interstrand cross-hnking. There is evidence that enzymatic reduction by a reduced nicotinamide-adenine dinucleotide phosphate (NADPH) dependent reductase is necessary to activate the drug. 

Tissue also contains some endogenous species that exhibit fluorescence, such as aromatic amino acids present in proteins (phenylalanine, tyrosine, and tryptophan), pyridine nucleotide enzyme cofactors (e.g., oxidized nicotinamide adenine dinucleotide, NADH pyridoxal phosphate flavin adenine dinucleotide, FAD), and cross-links between the collagen and the elastin in extracellular matrix.100 These typically possess excitation maxima in the ultraviolet, short natural lifetimes, and low quantum yields (see Table 10.1 for examples), but their characteristics strongly depend on whether they are bound to proteins. Excitation of these molecules would elicit background emission that would contaminate the emission due to implanted sensors, resulting in baseline offsets or even major spectral shifts in extreme cases therefore, it is necessary to carefully select fluorophores for implants. It is also noteworthy that the lifetimes are fairly short, such that use of longer lifetime emitters in sensors would allow lifetime-resolved measurements to extract sensor emission from overriding tissue fluorescence. 

Organometallic antineoplastics (platinum coordination complexes) also cross-link DNA, and many do so by binding to adjacent guanine nucleotides, called diguanosine dinucleotides, on a single strand of DNA. This leads to intrastrand DNA cross-linking. The anionic phosphate group on a second strand of DNA stabilizes... 

Deoxycytidinyl)methyl radical (98) was produced from the respective phenyl sulfide (99) via 254 nm photolysis. Initial studies in dinucleotides revealed that 98 adds to the C8-position of dG to form intrastrand cross-linked products (Scheme 41). These products were also observed when 98 was generated from 99 in chemically synthesized oligonucleotides, and when DNA was subjected to y-radiolysis. In DNA, 100 is favored over 101 and is even detected, albeit in almost 20-fold lower yield when 98 is generated under aerobic conditions. 

CLEA Cross-linked enzyme aggregate NADH dinucleotide... 

MSNT has been used for the sohd-phase synthesis of oligonucleotides on cross-linked polystyrene (eq 6). Best coupling result can be obtained by adding NMI as a catalyst, which not only increases the average condensation yield but also allows the dinucleotide phosphate to be coupled to the 5 -OH group of the growing oligonucleotide chain on the solid support. 

The identification of DNA as a primary target for metal-based drugs, especially cisplatin, has focused attention on the interactions of metal complexes with nucleic acid constituents, which include the simple purine and pyrimidine bases and their nucleoside and nucleotide derivatives. The structures, with abbreviations, are represented in Appendix 1. Simple complexes can represent models for cross links in DNA, which can be studied in more detail with small polynucleotides, from the simpler dinucleotides to oligonucleotides and this topic is covered in Section 4.4. There has been extensive use of substituted purines and pyrimidines as models for the DNA bases and in the examination of steric and electronic effects. The structures of many of these analogues are also collected in Appendix 1. 

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