Modular Synthesis of Methyl-Substituted Novel Psoralen N-Hydroxysuccinimide Esters and Evaluation of DNA Photocrosslinking Properties of the Corresponding Triplex-Forming Oligonucleotide Conjugates

Abstract

Psoralen-conjugated triplex-forming oligonucleotides (Ps-TFOs) have been used to induce DNA mutations or to suppress gene expression through the formation of crosslinked products with DNA in a sequence-specific manner. Psoralen can crosslink with DNA at its furan-ring and/or pyrone-ring side, yielding either a monoadduct or diadduct (interstrand crosslinking) product. The differences in the crosslinked structures of Ps-TFOs with the target DNAs are closely related to the changes in the biological outcomes induced by the Ps-TFOs. However, only a few reports have discussed the photocrosslinking properties of Ps-TFOs. The photocrosslinking properties of Ps-TFOs with structurally diverse psoralen derivatives remain elusive. Herein, we report the modular synthesis of novel methyl-substituted psoralen N-hydroxysuccinimide (NHS) esters. By using these esters, the effect of the methyl substituent of psoralen on the photocrosslinking of the corresponding Ps-TFOs was examined. The amount of the diadduct product was significantly reduced in the presence of methyl substituents at the C-3 and C-4 positions, while the total amount of photocrosslinking product was maintained. This work demonstrates the possibility of controlling the crosslinked product of Ps-TFOs by introducing methyl groups into psoralen: this ability to manipulate the product is an important factor in the biological applications of Ps-TFOs.

Key words

psoralen - triplex-forming oligonucleotides - modular synthesis - substituent effect - photocrosslinking - DNA crosslinking

Publikationsverlauf

Eingereicht: 24. November 2023

Angenommen nach Revision: 14. Dezember 2023

Accepted Manuscript online:
14. Dezember 2023

Artikel online veröffentlicht:
05. Februar 2024

• References and Notes

• 1a Pathirana D, Ormerod A, Saiag P, Smith C, Spuls P, Nast A, Barker J, Bos J, Burmester G.-R, Chimenti S, Dubertret L, Eberlein B, Erdmann R, Ferguson J, Girolomoni G, Gisondi P, Giunta A, Griffiths C, Hönigsmann H, Hussain M, Jobling R, Karvonen S.-L, Kemeny L, Kopp I, Leonardi C, Maccarone M, Menter A, Mrowietz U, Naldi L, Nijsten T, Ortonne J.-P, Orzechowski H.-D, Rantanen T, Reich K, Reytan N, Richards H, Thio H, Van De Kerkhof P, Rzany B. J. Eur. Acad. Dermatol. Venereol. 2009; 23 (Suppl. 02) : 1
• 1b Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, Gottlieb A, Koo JY. M, Lebwohl M, Lim HW, Van Voorhees AS, Beutner KR, Ryan C, Bhushan R. J. Am. Acad. Dermatol. 2010; 62: 114
• 2 Sidbury R, Davis DM, Cohen DE, Cordoro KM, Berger TG, Bergman JN, Chamlin SL, Cooper KD, Feldman SR, Hanifin JM, Krol A, Margolis DJ, Paller AS, Schwarzenberger K, Silverman RA, Simpson EL, Tom WL, Williams HC, Elmets CA, Block J, Harrod CG, Begolka WS, Eichenfield LF. J. Am. Acad. Dermatol. 2014; 71: 327
• 3a Taieb A, Alomar A, Böhm M, Dell’Anna ML, De Pase A, Eleftheriadou V, Ezzedine K, Gauthier Y, Gawkrodger DJ, Jouary T, Leone G, Moretti S, Nieuweboer-Krobotova L, Olsson MJ, Parsad D, Passeron T, Tanew A, van der Veen W, van Geel N, Whitton M, Wolkerstorfer A, Picardo M. Br. J. Dermatol. 2013; 168: 5
• 3b Oiso N, Suzuki T, Wataya-kaneda M, Tanemura A, Tanioka M, Fujimoto T, Fukai K, Kawakami T, Tsukamoto K, Yamaguchi Y, Sano S, Mitsuhashi Y, Nishigori C, Morita A, Nakagawa H, Mizoguchi M, Katayama IJ. Dermatol. 2013; 40: 344
• 4a Olsen EA, Hodak E, Anderson T, Carter JB, Henderson M, Cooper K, Lim HW. J. Am. Acad. Dermatol. 2016; 74: 27
• 4b Knobler R, Berlin G, Calzavara-Pinton P, Greinix H, Jaksch P, Laroche L, Ludvigsson J, Quaglino P, Reinisch W, Scarisbrick J, Schwarz T, Wolf P, Arenberger P, Assaf C, Bagot M, Barr M, Bohbot A, Bruckner-Tuderman L, Dreno B, Enk A, French L, Gniadecki R, Gollnick H, Hertl M, Jantschitsch C, Jung A, Just U, Klemke CD, Lippert U, Luger T, Papadavid E, Pehamberger H, Ranki A, Stadler R, Sterry W, Wolf IH, Worm M, Zic J, Zouboulis CC, Hillen U. J. Eur. Acad. Dermatol. Venereol. 2014; 28 (Suppl. 01) 1
• 5a Kitamura N, Kohtani S, Nakagaki R. J. Photochem. Photobiol., C 2005; 6: 168
• 5b Buhimschi DA, Gooden MD, Jing H, Fels RD, Hansen SK, Beyer FW, Dewhirst WM, Walder H, Gasparro PF. Photochem. Photobiol. 2020; 96: 1014
• 5c Cimino GD, Gamper HB, Isaacs ST, Hearst JE. Annu. Rev. Biochem. 1985; 54: 1151
• 5d Bissonnette L, Arnason JT, Smith ML. Photochem. Anal. 2008; 19: 342
• 5e Raunlo H, Pentikäinen O, Juvonen RO. Int. J. Mol. Sci. 2020; 21: 4708
• 6 Vowels BR, Yoo EK, Gasparro FP. Photochem. Photobiol. 1996; 63: 572
• 7a Ben-Hur E, Song P.-S. Adv. Radiat. Biol. 1984; 2: 131
• 7b Parrish JA, Stern RS, Pathak MA, Fitzpatrick TB. In The Science of Photomedicine . Regan JD, Parrish JA. Plenum Press; New York: 1982: 595
• 8 Rodighiero G, Dall’Acqua F, Averbeck D. In Psoralen DNA Photobiology, Vol. 1. Gasparro FP. CRC Press; Boca Raton: 1989: 37
• 9a Barre F.-X, Ait-Si-Ali S, Giovannangeli C, Luis R, Robin P, Pritchard LL, Hélène C, Harel-Bellan A. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 3084
• 9b Luo Z, Macris MA, Fawad Faruqi A, Glazer PM. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 9003
• 9c Vasquez KM, Dagle JM, Weeks DL, Glazer PM. J. Biol. Chem. 2001; 276: 38536
• 9d Puri N, Majumdar A, Cuenoud B, Miller PS, Seidman MM. Biochemistry. 2004; 43: 1343
• 9e Seidman MM, Puri N, Majumdar A, Cuenoud B, Miller PS, Alam R. Ann. N. Y. Acad. Sci. 2005; 1058: 119
• 9f Richards S, Liu S.-T, Majumdar A, Liu J.-L, Nairn RS, Bernier M, Maher V, Seidman MM. Nucleic Acids Res. 2005; 33: 5382
• 9g Majumdar A, Muniandy PA, Liu J, Liu J.-l, Liu S.-T, Cuenoud B, Seidman MM. J. Biol. Chem. 2008; 283: 11244
• 9h Semenyuk A, Darian E, Liu J, Majumdar A, Cuenoud B, Miller PS, MacKerell AD. Jr, Seidman MM. Biochemistry 2010; 49: 7867
• 10a Duval-Valentin G, Thuong NT, Hélène C. Proc. Natl. Acad. Sci. U. S. A. 1992; 89: 504
• 10b Grigoriev M, Praseuth D, Guievsse AL, Robin P, Thuong NT, Hélène C, Harel-Bellan A. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 3501
• 10c Ebbinghaus SW, Fortinberry H, Gamper HB. Jr. Biochemistry 1999; 38: 619
• 10d Faria M, Wood CD, Perrouault L, Nelson JS, Winter A, White MR. H, Hélène C, Giovannangeli C. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 3862
• 10e Diviacco S, Rapozzi V, Xodo L, Hélène C, Quadrifoglio F, Giovannangeli C. FASEB J. 2001; 15: 2660
• 10f Besch R, Giovannangeli C, Kammerbauer C, Degitz K. J. Biol. Chem. 2002; 277: 32473
• 10g Besch R, Marschall C, Schuh T, Giovannangeli C, Kammerbauer C, Degitz K. J. Invest. Dermatol. 2004; 122: 1114
• 10h Mikame Y, Eshima H, Toyama H, Nakao J, Matsuo M, Yamamoto T, Hari Y, Komano JA, Yamayoshi A. ChemMedChem. 2023; e202300348
• 11a Graham MK, Miller PS. JBIC J. Biol. Inorg. Chem. 2012; 17: 1197
• 11b Graham MK, Brown TR, Miller PS. Biochemistry 2015; 54: 2270
• 12 Diekmann J, Gontcharov J, Fröbel S, Ziegenbein CT, Zinth W, Gilch P. J. Am. Chem. Soc. 2019; 141: 13643
• 13 Otsuki T. Yuki Gosei Kagaku Kyokaishi 1991; 49: 809
• 14 Kanne D, Rapoport H, Hearst JE. J. Med. Chem. 1984; 27: 531
• 15 Nakao J, Mikame Y, Eshima H, Yamamoto T, Dohno C, Wada T, Yamayoshi A. ChemBioChem 2023; 24: e202200789
• 16 Melliou E, Magiatis P, Mitaku S, Skaltsounis A.-L, Chinou E, Chinou I. J. Nat. Prod. 2005; 68: 78
• 17 Ma T, Liu L, Xue H, Li L, Han C, Wang L, Chen Z, Liu G. J. Med. Chem. 2008; 51: 1432
• 18a Chimichi S, Boccalini M, Cosimelli B, Viola G, Vedaldi D, Dall’Acqua F. Tetrahedron 2002; 58: 4859
• 18b Roux D, Makki S, Bévalot F, Humbert P. Synlett 2007; 129
• 19 Oda K, Nishizono N, Tamai Y, Yamaguchi Y, Yoshimura T, Wada K, Machida M. Heterocycles 2005; 65: 1985