Cytosine applications

A common way to benefit from the ability to combine different molecular orbital methods in ONIOM is to combine a DFT or ab-initio description of the reactive region with a semi-empirical treatment of the immediate protein environment, including up to 1000 atoms. Due to the requirement for reliable semi-empirical parameters, as discussed in Section 2.2.1, this approach has primarily been used for non-metal or Zn-enzymes. Examples include human stromelysin-1 [83], carboxypeptidase [84], ribonucleotide reductase (substrate reaction) [85], farnesyl transferase [86] and cytosine deaminase [87], Combining two ab-initio methods of different accuracy is not common in biocatalysis applications, and one example from is an ONIOM (MP2 HF) study of catechol O-methyltransferase [88],... 

Valiev M, Kowalski K (2006) Hybrid coupled cluster and molecular dynamics approach Application to the excitation spectrum of cytosine in the native DNA environment. J Chem Phys 125 211101... 

These definitions apply to any atomic system, molecule or crystal. Fig. 7.3 a illustrates their application to the charge distribution of the guanine-cytosine base-pair. Fig. 7.3 b shows the molecular structure defined by the bond paths and the associated CPs that clearly and uniquely define the three hydrogen bonds that link the two bases. Fig. 7.3 c shows the atomic boundaries and bond paths overlaid on the electron density in the plane of the nuclei. All properties of the atoms can be determined, enabling one, for example, to determine separately the energy of formation of each of the three hydrogen bonds. 

In the case study discussed below [60], part of our ongoing interest in the application of DFT reactivity descriptors to biosystems [61-66], the interaction between cytosine and substituted benzenes is studied. Cytosine, a nucleobase derived from pyridine, was chosen because of its small size and because it possesses both a nitrogen and an oxygen atom as H-bond acceptors sites. 

Rentsch KM, et al. Pharmacokinetics of N" -octadecyl-l-P-D-arabinofuranosyI-cytosine (NOAC) in plasma and whole blood after intravenous and oral application in Mice. J Pharm Pharmacol 1997 49 1076. 

An attempt has been made to apply the Cohen and Reiss theory to dimer and hydrate formation in RNA.158 The results were inconclusive, probably because of a poor choice of example. Application of the theory to RNA was complicated by the necessity of estimating the distribution of uracil residues on the chain. The results are made still more tentative by the fact that Tanaka ignored the probability of dimer formation between cytosine residues, mixed dimers between cytosine and uracil, and hydrate formation in cytosine as well as the resultant deamination phenomena. A better choice of example would have been poly-uridylic acid. 

In 1961 it was reported that human leukocytes were capable of producing IFN in response to viral infections [8,9]. This viral stimulation of white blood cells was initially used to produce leukocyte IFN for clinical applications. Identification of a number of varied IFN inducers such as mycoplasma or other microorganisms in cell cultures, lipopolysaccharides (LPS, derived from bacteria membranes), tumor-derived or virus-transformed cells, and synthetic chemical compounds such as polyanions and poly I C (poly inosine-cytosine) suggested that different IFN mixtures could be derived from interaction of various inducing agents and appropriate target cells [10-16]. Another pH-labile, nonvirus-induced IFN termed immune-IFN (induced by immune effector cells) was discovered in 1965. It was produced by... 

UV spectroscopy is a sensitive tool for the elucidation of structures of molecules only if the different tautomers have distinct spectra. In some cases, cytosine or cytidine and their alkylated analogs have similar spectra with seriously overlapping bands, and thus the application of UV spectroscopy to the elucidation of the tautomeric structures of the molecules is inconclusive. In particular, the method is unreliable for the determination of tautomeric equilibria of cytosine (see below). Nevertheless the UV absorption spectra confirm the conclusions drawn from other studies as to the main form of cytosine and cytidine in aqueous solution at room temperature. 

The ground-state wave function of cytosine has been calculated by practically all the semiempirical as well as nonempirical methods. Here, we shall discuss the application of these methods to interpret the experimental quantities that can. be calculated from the molecular orbitals of cytosines and are related to the distribution of electron densities in the molecules. The simplest v-HMO method yielded a great mass of useful information concerning the structure and the properties of biological molecules including cytosines. The reader is referred to the book1 Quantum Biochemistry for the application of this method to interpret the physicochemical properties of biomolecules. Here we will restrict our attention to the results of the v-SCF MO and the all-valence or all-electron treatments of cytosines. 

Until recently the lactol ring structure of 2-desoxy-D-ribose in nucleic acid had been proved conclusively only for the thymidine nucleoside component and in this case it was furanose in form.26 Subsequently Brown and Lythgoe,27 by application of the periodate oxidation procedure to the 2 -desoxy ribosides of guanine, hypoxanthine, cytosine and thymine, afforded proof of the presence of a furanose sugar in each compound. 

G. Dryhurst and P.J. Elving, Electrochemical oxidation-reduction paths for pyrimidine, cytosine, purine and adenine. Correlation and application, Talanta, 16 (1969) 855-874. 

Cotton R, Rodrigues NR, Campbell RD. Reactivity of cytosine and thymine in single-base-pair mismatches with hydroxylamine and osmium tetroxide and its application to the study of mutations. Proc Natl Acad Sci USA 1988 85 4397-4401. 

The intramolecular Heck reaction is a powerful method for the synthesis of constrained tertiary and quaternary carbon centers and has been applied as a key step in the synthesis of a number of pyridine alkaloids. Mann et al. have accessed the bicyclononane core structure of huperzine A 150 in moderate yield by intramolecular Heck reaction of bromopyridine 151 (Equation 117). Another notable application of this methodology is the intramolecular a-arylation of the amide enolate generated from 152 to give the carbon skeleton of cytosine <20040BC1825> (Equation 118). 

The intramolecular photodimerization and [2 + 2]-photocycloaddition in DNA involves thymine or cytosine as the chromophore. This chemistry has been intensively investigated with regards to DNA damage and repair [131]. Despite the fact that the area is of continuous interest [132], the synthetic applications are limited and are not covered here in detail. However, some preparative aspects of 4-pyrimidinone photocycloaddition chemistry will be addressed. Aitken et al. have prepared a plethora of constrained cyclobutane P-amino acids by intra- or intermolecular [2 + 2]-photocycloaddition to uracil and its derivatives [133, 134]. In a chiral adaptation of this method, the uracil-derived enone 140 was employed to prepare the diastereomeric cyclobutanes 141 in very good yield (Scheme 6.49). The compounds are easily separated and were - despite the relatively low auxiliary-induced diastereoselectivity - well suited to prepare the as-2-aminocyclobutanecarboxylic acids 142 in enantiomerically pure form. Enantioselective access to the corresponding trans-products was feasible by epimerization in a-position to the carboxyl group [135],... 

A comparison of aliphatic amides, cyclic amides, cyclic imides and 2,4-dioxopyrimidines (uracils) in their deprotonated and diplatinated form (Scheme 4) reveals an increasing steric shielding of the V-bonded Pt ion (Ptx). With respect to formation of stacked and partially oxidized dinuclear species, it is evident that application of the binding principles seen in the blues of cyclic amides to the uracils and imides allows for tetranuclear species only. On the other hand, the presence of an additional O-donor in the imides and uracils (and likewise the cytosines, vide infra) provides an... 

In 1985, Lyamichev et al. [15] called H-DNA to the intramolecular triplex of sequence PyPuPy in order to indicate the high H+ concentration of the media where this triplex exists. This requires protonation of one cytosine in each base-triplet and the two pyrimidine strands must run antiparallel. These form has undergone much research recently [16, 17], as it is very important to understand what is the role of triplex DNA in the nucleic acid characteristics and biotechnological applications may be of great relevance. 

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