Playing Around with the Size and Shape of Quinolizinium ­Derivatives: Versatile Ligands for Duplex, Triplex, Quadruplex and Abasic Site-Containing DNA

This paper is dedicated to Professor Siegfried Hünig, University of Würzburg, on the occasion of his 95th birthday.

Abstract

The association of heteroaromatic ligands with DNA is an important and biologically relevant process, because it may have a strong influence on the function of the nucleic acid. As a result, efficient and selective DNA-targeting ligands are considered as promising lead structures for drugs. In this context, we established the quinolizinium ion as a versatile building block for the design of DNA-binding ligands, with the long-term goal to evaluate and understand the structural parameters that govern the association of cationic hetarenes with DNA. In this account we demonstrate that annelated quinolizinium derivatives are easily available and that their structure and substitution pattern are highly variable. Most notably, the availability of several derivatives with different size and shape enables the assessment of structure–property relationships regarding their DNA-binding properties. It is shown with exemplary case studies that the systematic variation of the ligand structure, along with analysis of the binding parameters, can be employed to analyze the structural requirements of a ligand to bind to different DNA forms, such as triplex, quadruplex and abasic site-containing DNA.

1 Introduction

2 Association of Quinolizinium Derivatives with Double-Stranded DNA

3 Association of Quinolizinium Derivatives with Triplex DNA

4 Association of Quinolizinium Derivatives with Quadruplex DNA

5 Association of Quinolizinium Derivatives with Abasic Positions in DNA

6 Conclusion

Key words

DNA binders - heterocycles - intercalators - polycyclic hetarenes - quinolizinium

• References


See for example:
• 1a Baumann B, Baxendale IR. Beilstein J. Org. Chem. 2013; 9: 2265
• 1b Modern Heterocyclic Chemistry . Alvarez-Builla J, Vaquero JJ, Barluenga J. Wiley-VCH; Weinheim: 2011
• 1c Heterocycles in Natural Product Synthesis . Majumdar KC, Chattopadhyay SK. Wiley-VCH; Weinheim, Germany: 2011
• 1d Joule JA, Mills K. Heterocyclic Chemistry . 5th ed. John Wiley & Sons; Chichester: 2010

See for example:
• 2a Heterocyclic Chemistry in Drug Discovery . Li JJ. John Wiley & Sons; Hoboken: 2013
• 2b Shiro T, Fukaya T, Tobe M. Eur. J. Med. Chem. 2015; 97: 397
• 2c Garg M, Chauhan M, Singh PK, Alex JM, Kumar R. Eur. J. Med. Chem. 2015; 97: 444
• 2d Rani R, Granchi C. Eur. J. Med. Chem. 2015; 97: 505
• 2e Sherer C, Snape TJ. Eur. J. Med. Chem. 2015; 97: 552
• 2f Küçükgüzel ŞG, Şenkardeş S. Eur. J. Med. Chem. 2015; 97: 816
• 3 The Top 50 Drugs of 2014, Chem. Eng. News, Supplement September 2014. ACS Publications; Washington: 2014. http://cenm.ag/censup030314 (accessed April 20, 2016)
• 4a Pett L, Hartley JA, Kiakos K. Curr. Topics Med. Chem. 2015; 15: 1293
• 4b Frezza M, Hindo S, Chen D, Davenport A, Schmitt S, Tomco D, Dou QP. Curr. Pharm. Des. 2010; 16: 1813

For selected reviews, see:
• 5a Rescifina A, Zagni C, Varrica MG, Pistara V, Corsaro A. Eur. J. Med. Chem. 2014; 74: 95
• 5b Banerjee S, Veale EB, Phelan CM, Murphy SA, Tocci GM, Gillespie LJ, Frimannsson DO, Kelly JM, Gunnlaugsson T. Chem. Soc. Rev. 2013; 42: 1601
• 5c Mukherjee A, Sasikala WD. Adv. Protein Chem. Struct. Biol. 2013; 92: 1
• 5d Wang X, Guo Z. Chem. Soc. Rev. 2013; 42: 202
• 5e Ihmels H, Thomas L In Materials Science of DNA Chemistry . Jin JI. CRC Press; Boca Raton: 2011: 49
• 5f Xie Y, Tam VK, Tor Y In The Chemical Biology of Nucleic Acids . Mayer G. John Wiley & Sons; Chichester: 2010: 115
• 5g Hannon MJ. Chem. Soc. Rev. 2007; 36: 280
• 5h Haq I In Nucleic Acids in Chemistry and Biology . Blackburn GM, Gait MJ, Loakes D, Williams DM. Royal Society of Chemistry; Cambridge: 2006: 341
• 5i Ihmels H, Otto D. Top. Curr. Chem. 2005; 258: 161
• 5j DNA and RNA Binders . Demeunynck M, Bailly C, Wilson WD. Wiley-VCH; Weinheim: 2002
• 6a Lerman LS. J. Mol. Biol. 1961; 3: 18
• 6b LePecq J.-B, Paoletti C. J. Mol. Biol. 1967; 27: 87
• 7a Pommier Y. ACS Chem. Biol. 2013; 8: 82
• 7b Mayer C, Janin YL. Chem. Rev. 2014; 114: 2313
• 7c Bailly C. Chem. Rev. 2012; 112: 3611
• 8 Neidle S, Thurston DE. InNucleic Acid Targeted Drug Design . Kerr DJ, Workman P. CRC Press; Boca Raton: 1994
• 9 Arai S, Hida M In Advances in Heterocyclic Chemistry . Katritzky AR. Academic Press, Inc; San Diego: 1992
• 10a Xiong Y.-X, Huang Z.-S, Tan J.-H. Eur. J. Med. Chem. 2015; 97: 538
• 10b Zhang L, Li J, Ma F, Yao S, Li N, Wang J, Wang Y, Wang X, Yao Q. Molecules 2012; 17: 11294
• 10c Bhadra K, Kumar GS. Biochim. Biophys. Acta 2011; 1810: 485
• 10d Maiti M, Kumar GS. J. Nucleic Acids 2010; 2010: Article ID 593408
• 10e Grycová L, Dostál J, Marek R, Bhadra K, Kumar GS. Phytochemistry 2007; 68: 150
• 11a Ihmels H, Faulhaber K, Vedaldi D, Dall’Acqua F, Viola G. Photochem. Photobiol. 2005; 81: 1107
• 11b Ihmels H, Faulhaber K, Viola G In Highlights in Bioorganic Chemistry: Methods and Applications . Schmuck C, Wennemers H. Wiley-VCH; Weinheim: 2004: 172
• 12a Vaquero JJ, Alvarez-Builla J In Modern Heterocyclic Chemistry . Alvarez-Builla J, Vaquero JJ, Barluenga J. Wiley-VCH; Weinheim: 2011: 1989
• 12b Ihmels H In Science of Synthesis Knowledge Updates 2011/1 . Thomas EJ. Georg Thieme Verlag; Stuttgart: 2011
• 12c Ihmels H In Science of Synthesis . Black DStC. Georg Thieme Verlag; Stuttgart: 2004
• 13 Denny WA In DNA and RNA Binders . Demeunynck M, Bailly C, Wilson WD. Wiley-VCH; Weinheim: 2002: 482

See for example:
• 14a Martinez V, Burgos C, Alvarez-Builla J, Fernandez G, Domingo A, Garcia-Nieto R, Gago F, Manzanares I, Cuevas C, Vaquero JJ. J. Med. Chem. 2004; 47: 1136
• 14b Martin MA, Bouin AS, Muñez-Botella S, del Castillo B. Polycyclic Aromat. Compd. 2002; 22: 37
• 14c Molina A, Vaquero JJ, Garcia Navio JL, Alvarez-Builla J, Pascual-Teresa B, Gago F, Rodrigo MM. J. Org. Chem. 1999; 64: 3907
• 14d Molina A, Vaquero JJ, Garcia Navio JL, Alvarez-Builla J, Rodrigo MM, Castano O, de Andres JL. Bioorg. Med. Chem. Lett. 1996; 6: 1453
• 14e Martin MA, del Castillo B, Lerner DA. Anal. Chim. Acta 1988; 205: 105
• 15 Tumir L.-M, Radić Stojković M, Piantanida I. Beilstein J. Org. Chem. 2014; 10: 2930
• 16a Bradsher CK, Beavers LE. J. Am. Chem. Soc. 1955; 77: 4812
• 16b Bradsher CK. Chem. Rev. 1946; 46: 447
• 17 Granzhan A, Ihmels H. ARKIVOC 2007; (viii): 136
• 18a Caneque T, Cuadro AM, Alvarez-Builla J, Vaquero JJ. Tetrahedron Lett. 2009; 50: 1419
• 18b Tian M, Ihmels H. Synthesis 2009; 4226
• 18c García-Cuadrado D, Cuadro AM, Barchín BM, Nuñez A, Cañeque T, Alvarez-Builla J, Vaquero JJ. J. Org. Chem. 2006; 71: 7989
• 18d García D, Cuadro AM, Alvarez-Builla J, Vaquero JJ. Org. Lett. 2004; 6: 4175
• 19a Faulhaber K, Granzhan A, Ihmels H, Otto D, Thomas L, Wells S. Photochem. Photobiol. Sci. 2011; 10: 1535
• 19b Tian M, Ihmels H, Brötz E. Dalton Trans. 2010; 39: 8195
• 19c Granzhan A, Ihmels H, Viola G. J. Am. Chem. Soc. 2007; 129: 1254
• 19d Faulhaber K, Granzhan A, Ihmels H, Viola G. Pure Appl. Chem. 2006; 78: 2325
• 19e Bohne C, Faulhaber K, Giese B, Häfner A, Hofmann A, Ihmels H, Köhler A.-K, Perä S, Schneider F, Sheepwash MA. L. J. Am. Chem. Soc. 2005; 127: 76
• 19f Ihmels H, Faulhaber K, Sturm C, Bringmann G, Messer K, Gabellini N, Vedaldi D, Viola G. Photochem. Photobiol. 2001; 74: 505
• 19g Ihmels H, Engels B, Faulhaber K, Lennartz C. Chem. Eur. J. 2000; 6: 2854
• 20 Viola G, Bressanini M, Gabellini N, Vedaldi D, Dall’Acqua F, Ihmels H. Photochem. Photobiol. Sci. 2002; 1: 882
• 21a Viola G, Dall’Acqua F, Gabellini N, Moro S, Vedaldi D, Ihmels H. ChemBioChem 2002; 3: 550
• 21b Ihmels H, Faulhaber K, Wissel K, Bringmann G, Messer K, Viola G, Vedaldi D. Eur. J. Org. Chem. 2001; 1157
• 22 Ihmels H, Otto D, Faccio A, Viola G. J. Org. Chem. 2006; 71: 8401
• 23 Basili S, Bergen A, Dall’Acqua F, Faccio A, Granzhan A, Ihmels H, Moro S, Viola G. Biochemistry 2007; 46: 12721
• 24 Yarmoluk SM, Lukashov SS, Ogul’chansky TY, Losytskyy MY, Kornyushyna OS. Biopolymers 2001; 62: 219
• 25a Suárez RM, Bosch P, Sucunza D, Cuadro AM, Domingo A, Mendicuti F, Vaquero JJ. Org. Biomol. Chem. 2015; 13: 527
• 25b Manna SK, Mandal A, Mondal SK, Adak AK, Jana A, Das A, Chattopadhyay S, Roy S, Ghorai SK, Samanta S, Hossain M, Baidya M. Org. Biomol. Chem. 2015; 13: 8037
• 26a Stiborova M, Frei E. Curr. Med. Chem. 2014; 21: 575
• 26b Froelich-Ammon SJ, Patchan MW, Osheroff N, Thompson RB. J. Biol. Chem. 1995; 270: 14998
• 26c Kohn KW, Waring MJ, Glaubiger D, Friedman CA. Cancer Res. 1975; 35: 71
• 27a Belotserkovskii BP, Mirkin SM, Hanawalt PC. Chem. Rev. 2013; 113: 8620
• 27b Buske FA, Mattick JS, Bailey TL. RNA Biol. 2011; 8: 427
• 28a Riechert-Krause F, Weisz K. Heterocycl. Commun. 2013; 19: 145
• 28b Saha R, Kumar GS. Chem. Biodivers. 2011; 8: 1512
• 28c Arya DP. Acc. Chem. Res. 2011; 44: 134
• 28d Song G, Ren J. Chem. Commun. 2010; 46: 7283
• 28e Fox KR, Darby RA. DNA and RNA Binders . Demeunynck M, Bailly C, Wilson WD. Wiley-VCH; Weinheim: 2002: 360
• 28f Jenkins TC. Curr. Med. Chem. 2000; 7: 99
• 29a Lee G.-J, Cho CB, Lee D.-J, Park J.-W, Kim SK. Bull. Korean Chem. Soc. 1999; 20: 653
• 29b Kan Y, Armitage B, Schuster GB. Biochemistry 1997; 36: 1461
• 29c Haq I, Ladbury JE, Chowdhry BZ, Jenkins TC. J. Am. Chem. Soc. 1996; 118: 10693
• 30a Wang LK, Rogers BD, Hecht SM. Chem. Res. Toxicol. 1996; 9: 75
• 30b Lee JS, Latimer LJ. P, Hampel KJ. Biochemistry 1993; 32: 5591
• 31 Vlieghe D, Van Meervelt L, Dautant A, Gallois B, Precigoux G, Kennard O. Science 1996; 273: 1702
• 32a Granzhan A, Ihmels H. ARKIVOC 2007; (viii): 136
• 32b Krapcho AP, Cadamuro SA, Macnee L. ARKIVOC 2007; (ix): 28
• 32c Granzhan A, Ihmels H, Mikhlina K, Deiseroth H.-J, Mikus H. Eur. J. Org. Chem. 2005; 4098
• 33a Fields DL, Miller JB, Reynolds DD. J. Org. Chem. 1965; 30: 252
• 33b Bradsher CK, Barker MW. J. Org. Chem. 1964; 29: 61
• 34 Bradsher CK, Sherer JP. J. Heterocycl. Chem. 1968; 5: 253
• 35 Fields DL, Regan TH. J. Heterocycl. Chem. 1973; 10: 195
• 36 Granzhan A, Bats JW, Ihmels H. Synthesis 2006; 1549
• 37a Sepiol J. Synthesis 1983; 559
• 37b Bailey AS, Bryant KC, Hancock RA, Morrell SH, Smith JC. J. Inst. Pet. 1947; 33: 503
• 37c Barnett EB, Sanders FG. J. Chem. Soc. 1933; 434
• 38 Mergny J.-L, Lacroix L. Oligonucleotides 2003; 13: 515
• 39 Chaires JB. Biopolymers 2015; 103: 473
• 40 Ihmels H, Otto D, Faccio A, Viola G. J. Org. Chem. 2006; 71: 8401
• 41a Basili S, Bergen A, Dall’Acqua F, Faccio A, Granzhan A, Ihmels H, Moro S, Viola G. Biochemistry 2007; 46: 12721
• 41b Granzhan A, Ihmels H. ChemBioChem 2006; 7: 1031
• 42 Strekowski L, Hojjat M, Wolinska E, Parker AN, Paliakov E, Gorecki T, Tanious FA, Wilson WD. Bioorg. Med. Chem. Lett. 2005; 15: 1097
• 43 Chaires JB, Ren J, Hamelberg D, Kumar A, Pandya V, Boykin DW, Wilson WD. J. Med. Chem. 2004; 47: 5729
• 44 Escudé C, Nguyen C.-H, Kukureti S, Janin Y, Sun J.-S, Bisagni E, Garestier T, Hélène C. Proc. Natl. Acad. Sci. USA 1998; 95: 3591
• 45 Teulade-Fichou M.-P, Perrin D, Boutorine A, Polverari D, Vigneron J.-P, Lehn JM, Sun J.-S, Garestier T, Hélène C. J. Am. Chem. Soc. 2001; 123: 9283
• 46 Baudoin O, Marchand C, Teulade-Fichou M.-P, Vigneron J.-P, Sun J.-S, Garestier T, Hélène C, Lehn J.-M. Chem. Eur. J. 1998; 4: 1504
• 47 Nguyen CH, Marchand C, Delage S, Sun J.-S, Garestier T, Hélène C, Bisagni E. J. Am. Chem. Soc. 1998; 120: 2501
• 48 Davis JT. Angew. Chem. Int. Ed. 2004; 43: 668
• 49a Quadruplex Nucleic Acids, In Topics in Current Chemistry . Vol. 330. Chaires JB, Graves D. Springer; Heidelberg: 2013
• 49b Parkinson GN In Quadruplex Nucleic Acids . Neidle S. RSC Publishing; Cambridge: 2006
• 49c Agarwala P, Pandey S, Maiti S. Org. Biomol. Chem. 2015; 13: 5570
• 50 Biffi G, Tannahill D, McCafferty J, Balasubramanian S. Nat. Chem. 2013; 5: 182
• 51 Sen D, Gilbert W. Nature 1988; 334: 364
• 52 Henderson E, Hardin CC, Walk SK, Tinoco IJr, Blackburn EH. Cell 1987; 51: 899
• 53a Sekaran V, Soares J, Jarstfer MB. J. Med. Chem. 2014; 57: 521
• 53b Majia B, Bhattacharya S. Chem. Commun. 2014; 50: 6422
• 54 Rhodes D, Lipps HJ. Nucleic Acids Res. 2015; 43: 8627
• 55a Ohnmacht SA, Neidle S. Bioorg. Med. Chem. Lett. 2014; 24: 2602
• 55b Biver T. Coord. Chem. Rev. 2013; 257: 2765
• 55c Chen JL.-Y, Sperry J, Ip NY, Brimble MA. Med. Chem. Commun. 2011; 2: 229
• 55d Monchaud D, Teulade-Fichou MP. Org. Biomol. Chem. 2008; 6: 627
• 56a Dzubiel D, Ihmels H, Mahmoud MM. A, Thomas L. Beilstein J. Org. Chem. 2014; 10: 2963
• 56b Jäger K, Bats JW, Ihmels H, Granzhan A, Uebach S, Patrick BO. Chem. Eur. J. 2012; 18: 10903
• 56c Granzhan A, Ihmels H, Jäger K. Chem. Commun. 2009; 1249
• 57a Gornall KC, Samosorn S, Tanwirat B, Suksamrarn A, Bremner JB, Kelso MJ, Beck JL. Chem. Commun. 2010; 46: 6602
• 57b Arora A, Balasubramanian C, Kumar N, Agrawal S, Ojha RP, Maiti S. FEBS J. 2008; 275: 3971
• 57c Galezowska E, Masternak A, Rubis B, Czyrski A, Rybczyńska M, Hermann TW, Juskowiak B. Int. J. Biol. Macromol. 2007; 41: 558
• 57d Franceschin M, Rossetti L, D’Ambrosio A, Schirripa S, Bianco A, Ortaggi G, Savino M, Schultes C, Neidle S. Bioorg. Med. Chem. Lett. 2006; 16: 1707
• 57e Juskowiak B, Galezowska E, Koczorowska N, Hermann TW. Bioorg. Med. Chem. Lett. 2004; 14: 3627
• 58 Bertrand H, Granzhan A, Monchaud D, Saettel N, Guillot R, Clifford S, Guédin A, Mergny J.-L, Teulade-Fichou MP. Chem. Eur. J. 2011; 17: 4529
• 59 Hou J.-Q, Tan J.-H, Wang XX, Chen S.-B, Huang S.-Y, Yan J.-W, Chen S.-H, Ou T.-M, Luo H.-B, Li D, Gu L.-Q, Huang ZS. Org. Biomol. Chem. 2011; 9: 6422
• 60 Kamada T, Wasada N. Synthesis 1990; 967
• 61 Pascal RA. Jr. Chem. Rev. 2006; 106: 4809
• 62a Stratford SA, Arhangelskis M, Bucar D.-K, Jones W. CrystEngComm 2014; 16: 10830
• 62b Ihmels H, Leusser D, Pfeiffer M, Stalke D. Mol. Cryst. Liq. Cryst. 2001; 356: 433
• 62c Ihmels H, Leusser D, Pfeiffer M, Stalke D. J. Org. Chem. 1999; 64: 5715
• 62d Wang WN, Jones W. Mol. Cryst. Liq. Cryst. 1994; 242: 227
• 62e Wang N, Jones W. Tetrahedron 1987; 43: 1273
• 62f Kearsley DK In Organic Solid State Chemistry . Desiraju GR. Elsevier; Amsterdam: 1987: 69
• 63a Renčiuk D, Zhou J, Beaurepaire L, Guédin A, Bourdoncle A, Mergny J.-L. Methods 2012; 57: 122
• 63b De Cian A, Guittat L, Kaiser M, Sacca B, Amrane S, Bourdoncle A, Alberti P, Teulade-Fichou M.-P, Lacroix L, Mergny J.-L. Methods 2007; 42: 183
• 64 Wang Y, Patel DJ. Structure 1993; 1: 263
• 65 Lim KW, Amrane S, Bouaziz S, Xu W, Mu Y, Patel DJ, Luu KN, Phan AT. J. Am. Chem. Soc. 2009; 131: 4301

See for example:
• 66a Li M.-H, Luo Q, Li Z.-S. J. Phys. Chem. B 2010; 114: 6216
• 66b Jia G, Feng Z, Wei C, Zhou J, Wang X, Li C. J. Phys. Chem. B 2009; 113: 16237
• 66c Zhang H.-J, Wang X.-F, Wang P, Ai X.-C, Zhang J.-P. Photochem. Photobiol. Sci. 2008; 7: 948
• 66d Parkinson GN, Ghosh R, Neidle S. Biochemistry 2007; 46: 2390
• 67 Jin B, Lee HM, Lee Y.-A, Ko JH, Kim C, Kim SK. J. Am. Chem. Soc. 2005; 127: 2417

See for example:
• 68a Hounsou C, Guittat L, Monchaud D, Jourdan M, Saettel N, Mergny J.-L, Teulade-Fichou M.-P. ChemMedChem 2007; 2: 655
• 68b Gavathiotis E, Heald RA, Stevens MF. G, Searle MS. J. Mol. Biol. 2003; 334: 25
• 68c Cocco MJ, Hanakahi LA, Huber MD, Maizels N. Nucleic Acids Res. 2003; 31: 2944
• 68d Kern JT, Thomas PW, Kerwin SM. Biochemistry 2002; 41: 11379
• 69 Constant J.-F, Demeunynck M In DNA and RNA Binders . Demeunynck M, Bailly C, Wilson WD. Wiley-VCH; Weinheim: 2002: 247
• 70 Schärer OD. Angew. Chem. Int. Ed. 2003; 42: 2946
• 71a Malina T, Scott P, Barec V. Nucleic Acids Res. 2015; 43: 5297
• 71b Kotera N, Poyer F, Granzhan A, Teulade-Fichou M.-P. Chem. Commun. 2015; 51: 15948

For a review, see:
• 72a Du YH, Huang J, Weng XC, Zhou X. Curr. Med. Chem. 2010; 17: 173

Naphthyridine derivatives:
• 72b Sato Y, Zhang Y, Seino T, Sugimoto T, Nishizawa S, Teramae N. Org. Biomol. Chem. 2012; 10: 4003
• 72c Wu F, Shao Y, Ma K, Cui QH, Liu GY, Xu S. Org. Biomol. Chem. 2012; 10: 3300

DNA intercalators such as proflavine:
• 72d Shao Y, Niu Z, Chen J, Zhang L. Chin. J. Chem. 2009; 27: 1117

Berberine derivatives:
• 72e Wu F, Shao Y, Ma K, Cui QH, Liu GY, Xu S. Org. Biomol. Chem. 2012; 10: 3300

Cyclic bisacridines:
• 72f Berthet N, Michon J, Lhomme J, Teulade-Fichou M.-P, Vigneron J.-P, Lehn J.-M. Chem. Eur. J. 1999; 5: 3625

Metalloinsertors:
• 72g Zeglis BM, Boland JA, Barton JK. J. Am. Chem. Soc. 2008; 130: 7530
• 72h McConnell AJ, Lim MH, Olmon ED, Song H, Dervan EE, Barton JK. Inorg. Chem. 2012; 51: 12511
• 73 Benner K, Granzhan A, Ihmels H, Viola G. Eur. J. Org. Chem. 2007; 4721
• 74 Bradsher CK, Parham JC. J. Heterocycl. Chem. 1964; 1: 30
• 75 Martelli A, Jourdan M, Constant JF, Demeunynck M, Dumy P. Bioorg. Med. Chem. Lett. 2006; 16: 154
• 76 Benner K, Ihmels H, Kölsch S, Pithan PM. Org. Biomol. Chem. 2014; 12: 1725

Effects of methyl groups in AP-DNA ligands:
• 77a Rajendar B, Rajendran A, Ye Z, Kanai E, Sato Y, Nishizawa S, Sikorski M, Teramae N. Org. Biomol. Chem. 2010; 8: 4949
• 77b Rajendar B, Rajendran A, Sato Y, Nishizawa S, Teramae N. Bioorg. Med. Chem. 2009; 17: 351
• 77c Sato Y, Nishizawa S, Yoshimoto K, Seino T, Ichihashi T, Morita K, Teramae N. Nucleic Acids Res. 2009; 37: 1411

Methyl effect in biochemistry:
• 78a Barreiro EJ, Kümmerle AE, Fraga CA. M. Chem. Rev. 2011; 111: 5215
• 78b Leung CS, Leung SS. F, Tirado-Rives J, Jorgensen WL. J. Med. Chem. 2012; 55: 4489
• 79a Mamalis P, Petrow V. J. Chem. Soc. 1950; 703
• 79b Buu-Hoi NP, Jaquignon P, Long CT. J. Chem. Soc. 1957; 505
• 80 Benner K, Bergen A, Ihmels H, Pithan PM. Chem. Eur. J. 2014; 20: 9883
• 81 Bergen A, Granzhan A, Ihmels H. Photochem. Photobiol. Sci. 2008; 7: 405
• 82a Badger GM, Sasse WH. F. J. Chem. Soc. 1957; 4
• 82b Staskun B. J. Org. Chem. 1964; 29: 2856
• 82c Chandler GS, Huppatz JL, Jones RA, Sasse WH. F. Aust. J. Chem. 1967; 20: 2037
• 83 Berthet N, Constant J.-F, Demeunynck M, Michon P, Lhomme J. J. Med. Chem. 1997; 40: 3346