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Targeting 24 bp Within Telomere Repeat Sequences with Tandem Tetramer Pyrrole–Imidazole Polyamide Probes

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Synthesis and Biological Evaluation of Pyrrole–Imidazole Polyamide Probes for Visualization of Telomeres

Part of the book series: Springer Theses ((Springer Theses))

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Abstract

Synthetic molecules that bind sequence-specifically to DNA have been developed for varied biological applications, including anticancer activity, regulation of gene expression, and visualization of specific genomic regions. Increasing the number of base pairs targeted by synthetic molecules strengthens their sequence specificity. Our group has been working on the development of pyrrole–imidazole polyamides that bind to the minor groove of DNA in a sequence-specific manner without causing denaturation. Recently, we reported a simple synthetic method of fluorescent tandem dimer polyamide probes composed of two hairpin moieties with a linking hinge, which bound to 12 bp in human telomeric repeats (5′–(TTAGGG)n–3′) and could be used to specifically visualize telomeres in chemically fixed cells under mild conditions. We also performed structural optimization and extension of the target base pairs to allow more specific staining of telomeres. In the present study, we synthesized tandem tetramer polyamides composed of four hairpin moieties, targeting 24 bp in telomeric repeats, the longest reported binding site for synthetic, non-nucleic-acid-based, sequence-specific DNA-binding molecules. The novel tandem tetramers bound with a nanomolar dissociation constant to 24 bp sequences made up of four telomeric repeats. Fluorescently labeled tandem tetramer polyamide probes could visualize human telomeres in chemically fixed cells with lower background signals than polyamide probes reported previously, suggesting that they had higher specificity for telomeres. Furthermore, high-throughput sequencing of human genomic DNA pulled down by the biotin-labeled tandem tetramer polyamide probe confirmed its effective binding to telomeric repeats in the complex chromatinized genome.

This chapter is reprinted and modified with permission from “Targeting 24 bp within Telomere Repeat Sequences with Tandem Tetramer Pyrrole–Imidazole Polyamide Probes” Kawamoto, Y.; Sasaki, A.; Chandran, A.; Hashiya, K.; Ide, S; Bando, T.; Maeshima, K; Sugiyama, H. J. Am. Chem. Soc. 2016, 138, 14100–14107. Copyright 2016 American Chemical Society.

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References

  1. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E (2012) Science 337:816–821

    Article  CAS  Google Scholar 

  2. Klug A (2010) Annu Rev Biochem 79:213–231

    Article  CAS  Google Scholar 

  3. Boch J, Scholze H, Schornack S, Landgraf A, Hahn S, Kay S, Lahaye T, Nickstadt A, Bonas U (2009) Science 326:1509–1512

    Article  CAS  Google Scholar 

  4. (a) Duca M, Vekhoff P, Oussedik K, Halby L, Arimondo PB (2008) Nucleic Acids Res 36:5123–5138. (b) Moser HE, Dervan PB (1987) Science 238:645–650

    Google Scholar 

  5. (a) Nielsen PE (2010) Chem Biodivers 7:786–804. (b) Nielsen PE, Egholm M, Berg RH, Buchardt O (1991) Science 254:1497–1500

    Google Scholar 

  6. (a) Liu Y, Chai Y, Kumar A, Tidwell RR, Boykin DW, Wilson WD (2012) J Am Chem Soc 134:5290–5299. (b) Paul A, Nanjunda R, Kumar A, Laughlin S, Nhili R, Depauw S, Deuser SS, Chai Y, Chaudhary AS, David–Cordonnier MH, Boykin DW, Wilson WD (2015) Bioorg Med Chem Lett 25:4927–4932

    Google Scholar 

  7. Rodríguez J, Mosquera J, García-Fandiño R, Vázquez ME, Mascareñas JL (2016) Chem Sci 7:3298–3303

    Article  Google Scholar 

  8. (a) Holman GG, Zewail–Foote M, Smith AR, Johnson KA, Iverson BL (2011) Nat Chem 3:875–881. (b) Smith AR, Iverson BL (2013) J Am Chem Soc 135:12,783–12,789

    Google Scholar 

  9. (a) Dervan PB (2001) Bioorg Med Chem 9:2215–2235. (b) Dervan PB, Edelson BS (2003) Curr Opin Struc Biol 13:284–299. (c) Dervan PB, Doss RM, Marques MA (2005) Curr Med Chem Anti–Cancer Agents 5:373–387. (d) Bando T, Sugiyama H (2006) Acc Chem Res 39:935–944. (e) Blackledge MS, Melander C (2013) Bioorg Med Chem 21:6101–6114. (f) Trauger JW, Baird EE, Dervan PB (1996) Nature 382:559–561. (g) White S, Szewczyk JW, Turner JM, Baird EE, Dervan PB (1998) Nature 391:468–471

    Google Scholar 

  10. (a) Herman DM, Baird EE, Dervan PB (1998) J Am Chem Soc 120:1382–1391. (b) Swalley SE, Baird EE, Dervan PB (1999) J Am Chem Soc 121:1113–1120

    Google Scholar 

  11. (a) Mrksich M, Parks ME, Dervan PB (1994) J Am Chem Soc 116:7983–7988. (b) de Clairac RPL, Geierstanger BH, Mrksich M, Dervan PB, Wemmer DE (1997) J Am Chem Soc 119:7909–7916

    Google Scholar 

  12. (a) Herman DM, Turner JM, Baird EE, Dervan PB (1999) J Am Chem Soc 121:1121–1129. (b) Chenoweth DM, Dervan PB (2009) Proc Natl Acad Sci U S A 106:13175–13179. (c) Chenoweth DM, Dervan PB (2010) J Am Chem Soc 132:14521–14529. (d) Morinaga H, Bando T, Takagaki T, Yamamoto H, Hashiya K, Sugiyama H (2011) J Am Chem Soc 133:18924–18930. (e) Li BC, Montgomery DC, Puckett JW, Dervan PB (2013) J Org Chem 78:124–133

    Google Scholar 

  13. (a) Parks ME, Baird EE, Dervan PB (1996) J Am Chem Soc 118:6147–6152. (b) Turner JM, Swalley SE, Baird EE, Dervan PB (1998) J Am Chem Soc 120:6219–6226

    Google Scholar 

  14. (a) Baird EE, Dervan PB (1996) J Am Chem Soc 118:6141–6146. (b) Wurtz NR, Turner JM, Baird EE, Dervan PB (2001) Org Lett 3:1201–1203. (c) Fan L, Yao G, Pan Z, Wu C, Wang HS, Burley GA, Su W (2015) Org Lett 17:158–161

    Google Scholar 

  15. (a) Vaijayanthi T, Bando T, Pandian GN, Sugiyama H (2012) ChemBioChem 13:2170–2185. (b) Boutorine AS, Novopashina DS, Krasheninina OA, Nozeret K, Venyaminova AG (2013) Molecules 18:15357–15397. (c) Nozeret K, Loll F, Escudé C, Boutorine AS (2015) ChemBioChem 16:549–554

    Google Scholar 

  16. (a) Anandhakumar C, Kizaki S, Bando T, Pandian GN, Sugiyama H (2015) ChemBioChem 16:20–38. (b) Meier JL, Yu AS, Korf I, Segal DJ, Dervan PB (2012) J Am Chem Soc 134:17814–17822. (c) Kang JS, Meier JL, Dervan PB (2014) J Am Chem Soc 136:3687–3694. (d) Erwin GS, Bhimsaria D, Eguchi A, Ansari AZ (2014) Angew Chem Int Ed 53:10124–10128. (e) Anandhakumar C, Li Y, Kizaki S, Pandian GN, Hashiya K, Bando T, Sugiyama H (2014) ChemBioChem 15:2647–2651. (f) Chandran A, Syed J, Taylor RD, Kashiwazaki G, Sato S, Hashiya K, Bando T, Sugiyama H (2016) Nucleic Acids Res 44:4014–4024. (g) Chandran A, Syed J, Li Y, Sato S, Bando T, Sugiyama H (2016) ChemBioChem 17:1905–1910

    Google Scholar 

  17. (a) Murty MSRC, Sugiyama H (2004) Biol Pharm Bull 27:468–474. (b) Gottesfeld JM, Neely L, Trauger JW, Baird EE, Dervan PB (1997) Nature 387:202–205. (c) Lai Y-M, Fukuda N, Ueno T, Kishioka H, Matsuda H, Saito S, Matsumoto K, Ayame H, Bando T, Sugiyama H, Mugishima H, Serie K (2005) J Pharmacol Exp Ther 315:571–575. (d) Hiraoka K, Inoue T, Taylor RD, Watanabe T, Koshikawa N, Yoda H, Shinohara K, Takatori A, Sugimoto K, Maru Y, Denda T, Fujiwara K, Balmain A, Ozaki T, Bando T, Sugiyama H, Nagase H (2015) Nat Commun 6:6706

    Google Scholar 

  18. (a) Xiao X, Yu P, Lim HS, Sikder D, Kodadek T (2007) Angew Chem Int Ed 46:2865–2868. (b) Patel S, Jung D, Yin P, Carlton P, Yamamoto M, Bando T, Sugiyama H, Lee KB (2014) ACS Nano 8:8959–8967

    Google Scholar 

  19. (a) Han L, Pandian GN, Junetha S, Sato S, Chandran A, Taniguchi J, Saha A, Bando T, Nagase H, Sugiyama H (2013) Angew Chem Int Ed 52:13410–13413. (b) Pandian GN, Taniguchi J, Junetha S, Sato S, Han L, Saha A, Anandhkumar C, Bando T, Nagase H, Vaijayanthi T, Taylor RD, Sugiyama H (2014) Sci Rep 4:3843. (c) Han L, Pandian GN, Chandran A, Sato S, Taniguchi J, Kashiwazaki G, Sawatani Y, Hashiya K, Bando T, Xu Y, Qian X, Sugiyama H (2015) Angew Chem Int Ed 54:8700–8703

    Google Scholar 

  20. Singh I, Wendeln C, Clark AW, Cooper JM, Ravoo BJ, Burley GA (2013) J Am Chem Soc 135:3449–3457

    Article  CAS  Google Scholar 

  21. (a) Trauger JW, Baird EE, Dervan PB (2014) J Am Chem Soc 120:3534–3535. (b) Yamamoto M, Bando T, Morinaga N, Kawamoto Y, Hashiya K, Sugiyama H (2014) Chem Eur J 20:752–759

    Google Scholar 

  22. (a) Herman DM, Baird EE, Dervan PB (1999) Chem Eur J 5:975–983. (b) Kers I, Dervan PB (2002) Bioorg Med Chem 10:3339–3349. (c) Schaal TD, Mallet WG, McMinn DL, Nguyen NV, Sopko MM, John S, Parekh BS (2018) Nucleic Acids Res 31:1282–1291. (d) Sasaki S, Bando T, Minoshima M, Shinohara K, Sugiyama H (2008) Chem Eur J 14:864–870. (e) Yamamoto M, Bando T, Kawamoto Y, Taylor R, Hashiya K, Sugiyama H (2014) Bioconjugate Chem 25:552–559. (f) Taylor RD, Kawamoto Y, Hashiya K, Bando T, Sugiyama H (2014) Chem. Asian J 9:2527–2533

    Google Scholar 

  23. (a) Maeshima K, Janssen S, Laemmli UK (2001) EMBO J 20:3218–3228. (b) Kawamoto Y, Bando T, Kamada F, Li Y, Hashiya K, Maeshima K, Sugiyama H (2013) J Am Chem Soc 135:16468–16477. (c) Hirata A, Nokihara K, Kawamoto Y, Bando T, Sasaki A, Ide S, Maeshima K, Kasama T, Sugiyama H (2014) J Am Chem Soc 136:11546–11554. (d) Kawamoto Y, Sasaki A, Hashiya K, Ide S, Bando T, Maeshima K, Sugiyama H (2015) Chem Sci 6:2307–2312. (e) Sasaki A, Ide S, Kawamoto Y, Bando T, Murata Y, Shimura M, Yamada K, Hirata A, Nokihara K, Hirata T, Sugiyama H, Maeshima K (2016) Sci Rep 6:29261

    Google Scholar 

  24. (a) Smogorzewska A, de Lange T (2004) Annu Rev Biochem 73:177–208. (b) Palm W, de Lange T (2008) Annu Rev Genet 42:301–334. (c) Blackburn EH (2010) Angew Chem Int Ed 49:7405–7421. (d) Xu Y (2011) Chem Soc Rev 40:2719–2740. (e) Nandakumar J, Cech TR (2013) Nat Rev Mol Cell Biol 14:69–82. (f) Zakian VA (2012) Exp Cell Res 318:1456–1460. (g) Smogorzewska A, van Steensel B, Bianchi A, Oelmann S, Schaefer MR, Schnapp G, de Lange T (2000) Mol Cell Biol 20:1659–1668

    Google Scholar 

  25. (a) Biffi G, Tannahill D, McCafferty J, Balasubramanian S (2013) Nat Chem 5:182–186. (b) Doksani Y, Wu JY, de Lange T, Zhuang X (2013) Cell 155:345–356

    Google Scholar 

  26. Lansdorp PM, Verwoerd NP, van de Rijke FM, Dragowska V, Little MT, Dirks RW, Raap AK, Tanke HJ (1996) Hum Mol Genet 5:685–691

    Article  CAS  Google Scholar 

  27. Anders L, Guenther MG, Qi J, Fan ZP, Marineau JJ, Rahl PB, Lovén J, Sigova AA, Smith WB, Lee TI, Bradner JE, Young RA (2014) Nat Biotechnol 32:92–96

    Article  CAS  Google Scholar 

  28. (a) Minoshima M, Bando T, Sasaki S, Fujimoto J, Sugiyama H (2008) Nucleic Acids Res 36:2889–2894. (b) Wetzler M, Wemmer DE (2010) Org Lett 12:3488–3490

    Google Scholar 

  29. (a) Lacy ER, Le NM, Price CA, Lee M, Wilson WD (2002) J Am Chem Soc 124:2153–2163. (b) Wang S, Aston K, Koeller KJ, Harris GD, Rath NP, Bashkin JK, Wilson WD (2014) Org Biomol Chem 12:7523–7536

    Google Scholar 

  30. (a) Feng J, Liu T, Qin B, Zhang Y, Liu XS (2012) Nat. Protoc 7:1728–1740. (b) Heinz S, Benner C, Spann N, Bertolino E, Lin YC, Laslo P, Cheng JX, Murre C, Singh H, Glass CK (2010) Mol Cell 38:576–589

    Google Scholar 

  31. (a) Maeshima K, Laemmli UK (2003) Dev Cell 4:467–480. (b) Maeshima K, Yahata K, Sasaki Y, Nakatomi R, Tachibana T, Hashikawa T, Imamoto F, Imamoto N (2006) J Cell Sci 119:4442–4451

    Google Scholar 

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  1. Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA

    Yusuke Kawamoto

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Correspondence to Yusuke Kawamoto .

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Kawamoto, Y. (2019). Targeting 24 bp Within Telomere Repeat Sequences with Tandem Tetramer Pyrrole–Imidazole Polyamide Probes. In: Synthesis and Biological Evaluation of Pyrrole–Imidazole Polyamide Probes for Visualization of Telomeres. Springer Theses. Springer, Singapore. https://doi.org/10.1007/978-981-13-6912-4_4

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