<sup>1</sup>H‐ and <sup>13</sup>C‐nmr studies on caffeine and its interaction with nucleic acids

Kan, Lou‐Sing; Borer, Philip N.; Cheng, Doris M.; Ts’o, Paul O. P.

doi:10.1002/bip.1980.360190908

Cited by 42 publications

(17 citation statements)

References 13 publications

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“…Instead, it strongly promotes nonspecific binding by UvrA as evidenced by the striking protection of the whole fragment (damaged or undamaged) from DNase I digestion when both UvrA and caffeine are present. We can also detect caffeine-dependent binding of (20)(21)(22), and it appears to affect the DNase I digestion pattern in our experiments in the same way that other intercalating compounds affect DNase I digestion: producing a sequence specific enhancement or inhibition of digestion (23,24). These caffeine-enhanced or inhibited digestion sites are indicated by asterisks in Figs.…”

Section: Resultsmentioning

confidence: 82%

Molecular mechanisms of DNA repair inhibition by caffeine.

Selby

Sancar

1990

Proc. Natl. Acad. Sci. U.S.A.

113

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Caffeine potentiates the mutagenic and lethal effects of genotoxic agents. It is thought that this is due, at least in some organisms, to inhibition of DNA repair. However, direct evidence for inhibition of repair enzymes has been lacking. Using purified Escherichia coli DNA photolyase and (A)BC excinuclease, we show that the drug inhibits photoreactivation and nucleotide excision repair by two different mechanisms. Caffeine inhibits photoreactivation by interfering with the specific binding of photolyase to damaged DNA, and it inhibits nucleotide excision repair by promoting nonspecific binding of the damage-recognition subunit, UvrA, of (A)BC excinuclease. A number of other intercalators, including acriflavin and ethidium bromide, appear to inhibit the excinuclease by a similar mechanism-that is, by trapping the UvrA subunit in nonproductive complexes on undamaged DNA.Caffeine has a myriad of pharmacological effects. Among these, the sensitization of cells to the lethal and mutagenic effects of DNA-damaging agents has been the subject of numerous studies in the last three decades (1-5). It has been suggested that caffeine binds to DNA-perhaps with higher affinity to damaged regions (6)-and thus interferes with the specific binding of repair enzymes (4). However, none of the repair proteins that have been purified and tested, Micrococcus luteus UV endonuclease (7), Escherichia coli 3-methyladenine DNA glycosylase I (8), and human placental AP endonuclease (9), were inhibited by caffeine. In E. coli, caffeine at 10-100 mM inhibits photoreactivation in vivo (3) and nucleotide excision repair in vivo (1) and in a permeabilized cell system (10).Photoreactivation is the reversal of the mutagenic and lethal effects of far UV by subsequent exposure of cells to near UV or visible light (11). The phenomenon is mediated by photoreactivating enzyme, DNA photolyase. This enzyme repairs DNA by breaking the cyclobutane ring of pyrimidine dimers (80-90%o of the total UV photoproducts) in a lightdriven reaction. The enzyme binds to pyrimidine dimers in a light-independent reaction and, upon absorbing a photon of photoreactivating light (300-500 nm), donates an electron to the dimer, initiating an electronic reorganization which eventually produces two intact pyrimidines (11). In contrast to photoreactivation, which repairs pyrimidine dimers in situ, nucleotide excision repair entails the removal of a segment of the DNA backbone containing the damaged base(s) followed by filling in of the gap by DNA polymerase and sealing by ligase. In addition to removing pyrimidine dimers, this repair mechanism is responsible for removal of DNA adducts of a wide variety of chemicals such as psoralen, cisplatin, and mitomycin C (11). In E. coli, nucleotide excision is initiated by an ATP-dependent nuclease, the (A)BC excinuclease,* which incises the eighth phosphodiester bond 5' and the fourth phosphodiester bond 3' to the adducted nucleotide(s). In this study we have used defined DNA substrates, purified photoreactivating enzyme, DNA ...

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Section: Resultsmentioning

confidence: 82%

Molecular mechanisms of DNA repair inhibition by caffeine.

Selby

Sancar

1990

Proc. Natl. Acad. Sci. U.S.A.

113

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“…( 54) actinomycin D, 55) theaflavin, 56) novatrone (mitoxantrone) 57,58) and aromatic drugs [59][60] have been studied by NMR spectroscopy. It has been suggested that the imidazole moiety of caffeine is involved in the interaction with aromatic species.…”

Section: Stability Constants Of Rf-caffeine Complexmentioning

confidence: 99%

Effect of Caffeine Complexation on the Photolysis of Riboflavin in Aqueous Solution: A Kinetic Study

Ahmad

Ahmed

Sheraz

et al. 2009

CHEMICAL & PHARMACEUTICAL BULLETIN

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1363Riboflavin is a highly photosensitive compound and is degraded in aqueous solution by several mechanisms [1][2][3] including intramolecular photoreduction 4,5) and intramolecular photoaddition. [6][7][8][9] These reactions are affected by pH, 4,5,[10][11][12] solvent polarity and viscosity, 13,14) ionic strength, 15) buffer kind and concentration [6][7][8][9]16) and light intensity and wavelengths. [6][7][8][9]17) Various methods including the use of photostabilizers, incorporation into liposomes and cyclodextrin complexation have been used to stabilize riboflavin solutions in the presence of light. [18][19][20][21] Another approach to achieve stabilization of drugs is through complexation with caffeine and other agents. [22][23][24][25][26] Riboflavin is known to form molecular complexes with caffeine [27][28][29][30][31][32] which has been found to influence the rate of its chemical 33) and photochemical degradation.17) Riboflavin-caffeine complexation may improve the bioavailability 34) and therapeutic activity 35) of the vitamin. NMR studies have been conducted to understand the nature of association between caffeine and flavin mononucleotide 36) that may help in the understanding of the mode of riboflavin stabilization. The present work is based on a detailed study of the kinetics of riboflavin photolysis in the presence of caffeine over a wide range of pH using a specific multicomponent spectrophotometric method 12) for the determination of riboflavin and photoproducts. The kinetic data have been used to determine the stability constants for riboflavin-caffeine complex. The quantitative and kinetic evaluation of such interactions may suggest the possibility of achieving the stabilization of photolabile compounds and thus enhance their biological action. The chemical structures of riboflavin, its photoproducts and caffeine are shown in Fig. 1. ExperimentalThe materials and methods used are the same as previously described for a similar study.5) The photolysis of 5ϫ10 Ϫ5 M riboflavin (RF) solutions was carried out in the presence of 0.5-2.5ϫ10Ϫ4 M caffeine using a Philips HPLN 125 W high pressure mercury vapor fluorescent lamp (emission at 405 and 435 nm) 9) as the irradiation source. The spectral measurements on RF and degraded solutions were performed on a Shimadzu UV-1601 recording spectrophotometer using silica cells of 10 mm path length. The intensity of the fluorescent lamp was determined by potassium ferrioxalate actinome- The effect of caffeine complexation with riboflavin on the kinetics of riboflavin photolysis in the pH range 2.0-10.5 has been studied. The photolysis of riboflavin solutions (5؋10 ؊ ؊5 M) was carried out in the presence of caffeine (0.5-2.5؋10 ؊ ؊4 M) using a visible radiation source. A specific multicomponent spectrophotometric method was used for the determination of riboflavin and photoproducts in photolysed solutions. The apparent first-order rate constants (k) for the photolysis reactions range from 2.71؋10 ؊4 to 4.26؋10 ؊2 min Effect of Caffeine Complexation on the Photol...

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“…However, the suggestion [19][20][21]23,[35][36][37][38][39][40] that hetero-association is the only mechanism for the protective effect in DrugInterceptor-Receptor systems is primary based on the assumption that the interceptor molecule does not (or very weakly) interact with the bio-receptor. On the other hand, it has been shown that both CAF [43,[59][60][61] and RBF [50] molecules are able to bind with DNA in a fashion very similar to intercalation or by external binding. A quantitative estimate of the DNA complexation constants gives the same order of magnitude as for the hetero-association constants with various drugs (~10 2 … 10 3 M − 1 for CAF [43] and~10 3 …10 4 M − 1 for RBF [50]).…”

Section: Introductionmentioning

confidence: 99%