Two-dimensional IR spectroscopy of the anti-HIV agent KP1212 reveals protonated and neutral tautomers that influence pH-dependent mutagenicity

Proceedings of the National Academy of Sciences of the United States of America

Volumn 112, Issue 11, 2015, Pages 3229-3234

  Peng, Chunte Sam ^a   Fedeles, Bogdan I ^a,b   Singh, Vipender ^a,b   Li, Deyu ^a,b   Amariuta, Tiffany ^b   Essigmann, John M ^a,b   Tokmakoff, Andrei ^c  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^b Massachusetts Institute of Technology Cambridge   (United States)

^c UNIVERSITY OF CHICAGO   (United States)

Author keywords

KP1461; Tautomerism; Time resolved spectroscopy; Viral decay acceleration

Indexed keywords

5,6 DIHYDRO 5 AZA 2' DEOXYCYTIDINE; ADENINE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; RESTRICTION ENDONUCLEASE; UNCLASSIFIED DRUG; 5,6-DIHYDRO-5-AZA-2'-DEOXYCYTIDINE; DEOXYCYTIDINE; DNA; PROTON; WATER;

ANTIVIRAL ACTIVITY; ARTICLE; DENSITY FUNCTIONAL THEORY; DRUG DESIGN; DRUG MECHANISM; DRUG STRUCTURE; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IN VITRO STUDY; INFRARED SPECTROSCOPY; MUTAGENESIS; MUTAGENICITY; MUTATION RATE; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PH; PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTON TRANSPORT; TAUTOMER; TAUTOMERIZATION; TEMPERATURE DEPENDENCE; VIRUS REPLICATION; ANALOGS AND DERIVATIVES; CHEMICAL STRUCTURE; CHEMISTRY; GENETICS; MOLECULAR GENETICS; MUTAGEN TESTING; MUTATION; NUCLEOTIDE SEQUENCE; QUANTUM THEORY; STEREOISOMERISM; TEMPERATURE;

ANTI-HIV AGENTS; BASE SEQUENCE; DEOXYCYTIDINE; DNA; HYDROGEN-ION CONCENTRATION; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MUTAGENICITY TESTS; MUTATION; PROTONS; QUANTUM THEORY; SPECTROSCOPY, FOURIER TRANSFORM INFRARED; STEREOISOMERISM; TEMPERATURE; WATER;

EID: 84925244300     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1415974112     Document Type: Article

References (33)

1. Eigen M (2002) Error catastrophe and antiviral strategy. Proc Natl Acad Sci USA 99(21):13374-13376.
2. Perales C, Martín V, Domingo E (2011) Lethal mutagenesis of viruses. Curr Opin Virol 1(5):419-422.
3. Bonnac LF, Mansky LM, Patterson SE (2013) Structure-activity relationships and design of viral mutagens and application to lethal mutagenesis. J Med Chem 56(23):9403-9414.
4. Loeb LA, et al. (1999) Lethal mutagenesis of HIV with mutagenic nucleoside analogs. Proc Natl Acad Sci USA 96(4):1492-1497.
5. Feig DI, Sowers LC, Loeb LA (1994) Reverse chemical mutagenesis: identification of the mutagenic lesions resulting from reactive oxygen species-mediated damage to DNA. Proc Natl Acad Sci USA 91(14):6609-6613.
6. Kreutzer DA, Essigmann JM (1998) Oxidized, deaminated cytosines are a source of C-> T transitions in vivo. Proc Natl Acad Sci USA 95(7):3578-3582.
7. Daifuku R (2003) Stealth nucleosides: mode of action and potential use in the treatment of viral diseases. BioDrugs 17(3):169-177.
8. Harris KS, Brabant W, Styrchak S, Gall A, Daifuku R (2005) KP-1212/1461, a nucleoside designed for the treatment of HIV by viral mutagenesis. Antiviral Res 67(1):1-9.
9. Murakami E, Basavapathruni A, Bradley WD, Anderson KS (2005) Mechanism of action of a novel viral mutagenic covert nucleotide: Molecular interactions with HIV-1 reverse transcriptase and host cell DNA polymerases. Antiviral Res 67(1):10-17.
10. Mullins JI, et al. (2011) Mutation of HIV-1 genomes in a clinical population treated with the mutagenic nucleoside KP1461. PLoS ONE 6(1):e15135.
11. Crotty S, et al. (2000) The broad-spectrum antiviral ribonucleoside ribavirin is an RNA virus mutagen. Nat Med 6(12):1375-1379.
12. Baranovich T, et al. (2013) T-705 (favipiravir) induces lethal mutagenesis in influenza A H1N1 viruses in vitro. J Virol 87(7):3741-3751.
13. Li D, et al. (2014) Tautomerism provides a molecular explanation for the mutagenic properties of the anti-HIV nucleoside 5-aza-5,6-dihydro-2'-deoxycytidine. Proc Natl Acad Sci USA 111(32):E3252-E3259.
14. Watson JD, Crick FH (1953) Genetical implications of the structure of deoxyribonucleic acid. Nature 171(4361):964-967.
15. Topal MD, Fresco JR (1976) Complementary base pairing and the origin of substitution mutations. Nature 263(5575):285-289.
16. Peng CS, Baiz CR, Tokmakoff A (2013) Direct observation of ground-state lactamlactim tautomerization using temperature-jump transient 2D IR spectroscopy. Proc Natl Acad Sci USA 110(23):9243-9248.
17. Kuhne RO, Schaffhauser T,Wokaun A, Ernst RR (1979) Study of transient chemical reactions by NMR. Fast stopped-flow Fourier transform experiments. J Magn Reson 35(1):39-67.
18. Miles HT (1961) Tautomeric forms in a polynucleotide helix and their bearing on the structure of DNA. Proc Natl Acad Sci USA 47:791-802.
19. Suen W, Spiro TG, Sowers LC, Fresco JR (1999) Identification by UV resonance Raman spectroscopy of an imino tautomer of 5-hydroxy-2'-deoxycytidine, a powerful base analog transition mutagen with a much higher unfavored tautomer frequency than that of the natural residue 2'-deoxycytidine. Proc Natl Acad Sci USA 96(8):4500-4505.
20. Messmer AT, Lippert KM, Schreiner PR, Bredenbeck J (2013) Structure analysis of substrate catalyst complexes in mixtures with ultrafast two-dimensional infrared spectroscopy. Phys Chem Chem Phys 15(5):1509-1517.
21. Peng CS, Tokmakoff A (2012) Identification of lactam-lactim tautomers of aromatic heterocycles in aqueous solution using 2D IR spectroscopy. J Phys Chem Lett 3(22):3302-3306.
22. Banyay M, Sarkar M, Gräslund A (2003) A library of IR bands of nucleic acids in solution. Biophys Chem 104(2):477-488.
23. La Francois CJ, Jang YH, Cagin T, Goddard WA, 3rd, Sowers LC (2000) Conformation and proton configuration of pyrimidine deoxynucleoside oxidation damage products in water. Chem Res Toxicol 13(6):462-470.
24. Peng CS, Jones KC, Tokmakoff A (2011) Anharmonic vibrational modes of nucleic acid bases revealed by 2D IR spectroscopy. J Am Chem Soc 133(39):15650-15660.
25. Siegfried NA, O'Hare B, Bevilacqua PC (2010) Driving forces for nucleic acid pK(a) shifting in an A(+).C wobble: Effects of helix position, temperature, and ionic strength. Biochemistry 49(15):3225-3236.
26. Lee C, Cho M (2006) Vibrational dynamics of DNA. II. Deuterium exchange effects and simulated IR absorption spectra. J Chem Phys 125(11):114509.
27. 2O complexes. J Chem Phys 118(8):3491-3498.
28. Delaney JC, Essigmann JM (2006) Assays for determining lesion bypass efficiency and mutagenicity of site-specific DNA lesions in vivo. Methods Enzymol 408:1-15.
29. Wang W, Hellinga HW, Beese LS (2011) Structural evidence for the rare tautomer hypothesis of spontaneous mutagenesis. Proc Natl Acad Sci USA 108(43):17644-17648.
30. Varani G, McClain WH (2000) The G x U wobble base pair. A fundamental building block of RNA structure crucial to RNA function in diverse biological systems. EMBO Rep 1(1):18-23.
31. Johnson SJ, Beese LS (2004) Structures of mismatch replication errors observed in a DNA polymerase. Cell 116(6):803-816.
32. Sowers LC, Shaw BR, Veigl ML, Sedwick WD (1987) DNA base modification: Ionized base pairs and mutagenesis. Mutat Res 177(2):201-218.
33. Obeid S, et al. (2010) Replication through an abasic DNA lesion: Structural basis for adenine selectivity. EMBO J 29(10):1738-1747.