Molecular basis for the DNA damage induction and anticancer activity of asymmetrically substituted anthrapyridazone PDZ-7
Abstract
nthrapyridazones, imino analogues of anthraquinone, constitute a family of compounds with remarkable anti-cancer activity. To date, over 20 derivatives were studied, of which most displayed nanomolar cytotoxicity towards broad spectrum of cancer cells, including breast, prostate and leukemic ones. BS-154, the most potent derivative, had IC50 values close to 1 nM, however, it was toxic in animal studies. Here, we characterize another anthrapyridazone, PDZ-7, which retains high cytotoxicity while being well tolerated in mice. PDZ-7 is also active in vivo against anthracycline-resistant tumor in a mouse xenograft model and induces DNA damage in proliferating cells, preferentially targeting cells in S and G2 phases of the cell cycle. Activation of Mre11-Rad50-Nbs1 (MRN) complex and phosphorylation of H2AX suggest double-stranded DNA breaks as a major consequence of PDZ-7 treatment. Consistent with this, PDZ-7 treatment blocked DNA synthesis and resulted in cell cycle arrest in late S and G2 phases. Analysis of topoisomerase IIα activity and isolation of the stabilized covalent topoisomerase IIα - DNA complex in the presence of PDZ-7 suggests that this compound is a topoisomerase IIα poison. Moreover, PDZ-7 interfered with actin polymerization, thereby implying its action as a dual inhibitor of processes critical for dividing cells. Using nuclear magnetic resonance (NMR) spectroscopy we show that PDZ-7 interacts with DNA double helix and quadruplex DNA structure. Taken together, our results suggest that PDZ-7 is a unique compound targeting actin cytoskeleton and DNA.
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- artykuł w czasopiśmie wyróżnionym w JCR
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Oncotarget
no. 10,
pages 105137 - 105154,
ISSN: 1949-2553 - Language:
- English
- Publication year:
- 2017
- Bibliographic description:
- Misiak M., Heldt M., Szeligowska M., Mazzini S., Scaglioni L., Grabe G., Serocki M., Lica J., Świtalska M., Wietrzyk J., Beretta G., Perego P., Ziętkowski D., Bagiński M., Borowski E., Składanowski A.: Molecular basis for the DNA damage induction and anticancer activity of asymmetrically substituted anthrapyridazone PDZ-7// Oncotarget. -Vol. 10, nr. 8 (2017), s.105137-105154
- DOI:
- Digital Object Identifier (open in new tab) 10.18632/oncotarget.21806
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-
- Cassinelli G. The roots of modern oncology: from discovery of new antitumor anthracyclines to their clinical use. Tumori J [Internet]. 2016; 2016: 226-35. https://doi.org/10.5301/ tj.5000507. open in new tab
- Nitiss JL. Targeting DNA topoisomerase II in cancer chemotherapy. Nat Rev Cancer. 2009; 9: 338-50. https:// doi.org/10.1038/nrc2607. www.impactjournals.com/oncotarget open in new tab
- Nitiss JL. DNA topoisomerase II and its growing repertoire of biological functions. Nat Rev Cancer. 2009; 9: 327-37. https://doi.org/10.1038/nrc2608. open in new tab
- Spence JM, Phua HH, Mills W, Carpenter AJ, Porter ACG, Farr CJ. Depletion of topoisomerase IIalpha leads to shortening of the metaphase interkinetochore distance and abnormal persistence of PICH-coated anaphase threads. J Cell Sci. 2007; 120: 3952-64. https://doi.org/10.1242/ jcs.013730. open in new tab
- Farr CJ, Antoniou-Kourounioti M, Mimmack ML, Volkov A, Porter ACG. The α isoform of topoisomerase II is required for hypercompaction of mitotic chromosomes in human cells. Nucleic Acids Res. 2014; 42: 4414-26. https:// doi.org/10.1093/nar/gku076. open in new tab
- Maede Y, Shimizu H, Fukushima T, Kogame T, Nakamura T, Miki T, Takeda S, Pommier Y, Murai J. Differential and common DNA repair pathways for topoisomerase I-and II-targeted drugs in a genetic DT40 repair cell screen panel. open in new tab
- Mol Cancer Ther [Internet]. 2014; 13: 214-20. https://doi. org/10.1158/1535-7163.MCT-13-0551. open in new tab
- Uziel T, Lerenthal Y, Moyal L, Andegeko Y, Mittelman L, Shiloh Y. Requirement of the MRN complex for ATM activation by DNA damage. EMBO J. 2003; 22: 5612-21. https://doi.org/10.1093/emboj/cdg541. open in new tab
- Bailly C. Contemporary challenges in the design of topoisomerase II inhibitors for cancer chemotherapy. Chem Rev [Internet]. 2012; 112: 3611-40. https://doi.org/10.1021/ cr200325f. open in new tab
- Zeman SM, Phillips DR, Crothers DM. Characterization of covalent adriamycin-DNA adducts. Proc Natl Acad Sci U S A [Internet]. 1998; 95: 11561-5. https://doi.org/10.1073/ pnas.95.20.11561. open in new tab
- Swift LP, Rephaeli A, Nudelman A, Phillips DR, Cutts SM. Doxorubicin-DNA adducts induce a non-topoisomerase II-mediated form of cell death. Cancer Res. 2006; 66: 4863- 71. https://doi.org/10.1158/0008-5472.CAN-05-3410. open in new tab
- Pang B, Qiao X, Janssen L, Velds A, Groothuis T, Kerkhoven R, Nieuwland M, Ovaa H, Rottenberg S, van Tellingen O, Janssen J, Huijgens P, Zwart W, et al. Drug- induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin. Nat Commun [Internet]. Nature Publishing Group; 2013; 4: 1908. https:// doi.org/10.1038/ncomms2921. open in new tab
- Ichikawa Y, Ghanefar M, Bayeva M, Wu R, Khechaduri A, Naga Prasad S V., Mutharasan RK, Jairaj Naik T, Ardehali H. Cardiotoxicity of doxorubicin is mediated through mitochondrial iron accumulation. J Clin Invest. 2014; 124: 617-30. https://doi.org/10.1172/JCI72931. open in new tab
- Cowell IG, Austin CA. Mechanism of generation of therapy related leukemia in response to anti-topoisomerase II agents. Int J Environ Res Public Health. 2012; 9: 2075-91. https://doi.org/10.3390/ijerph9062075. open in new tab
- Cowell IG, Sondka Z, Smith K, Lee KC, Manville CM, Sidorczuk-Lesthuruge M, Rance HA, Padget K, Jackson GH, Adachi N, Austin CA. Model for MLL translocations in therapy-related leukemia involving topoisomerase IIβ- mediated DNA strand breaks and gene proximity. Proc Natl Acad Sci U S A [Internet]. 2012; 109: 8989-94. https://doi. org/10.1073/pnas.1204406109. open in new tab
- Zhang S, Liu X, Bawa-Khalfe T, Lu L-S, Lyu YL, Liu LF, Yeh ETH. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med [Internet]. open in new tab
- Nature Publishing Group; 2012; 18. https://doi.org/10.1038/ nm.2919. open in new tab
- O'Brien MER, Wigler N, Inbar M, Rosso R, Grischke E, Santoro A, Catane R, Kieback DG, Tomczak P, Ackland SP, Orlandi F, Mellars L, Alland L, et al. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX TM /Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004; 15: 440-9. https://doi.org/10.1093/annonc/mdh097. open in new tab
- Toyoda E, Kagaya S, Cowell IG, Kurosawa A, Kamoshita K, Nishikawa K, Iiizumi S, Koyama H, Austin CA, Adachi N. NK314, a topoisomerase II inhibitor that specifically targets the ?? isoform. J Biol Chem. 2008; 283: 23711-20. https://doi.org/10.1074/jbc.M803936200. open in new tab
- Gao H, Huang K, Yamasaki EF, Chan KK, Snapka RM, Gao H, Huang K, Yamasaki EF, Chan KK, Chohan L, Snapka RM. XK469, a Selective Topoisomerase IIβ Poison. 1999; 96: 12168-73. open in new tab
- Skladanowski a, Plisov SY, Konopa J, Larsen a K. Inhibition of DNA topoisomerase II by imidazoacridinones, new antineoplastic agents with strong activity against solid tumors. Mol Pharmacol. 1996; 49: 772-80.
- Isambert N, Campone M, Bourbouloux E, Drouin M, Major A, Yin W, Loadman P, Capizzi R, Grieshaber C, Fumoleau P. Evaluation of the safety of C-1311 (SYMADEX) administered in a phase 1 dose escalation trial as a weekly infusion for 3 consecutive weeks in patients with advanced solid tumours. Eur J Cancer [Internet]. open in new tab
- Elsevier Ltd; 2010; 46: 729-34. https://doi.org/10.1016/j.ejca.2009.12.005. open in new tab
- Stefańska B, Arciemiuk MS, Bontemps-Gracz MM, Dzieduszycka M, Kupiec A, Martelli S, Borowski E. Synthesis and biological evaluation of 2,7-Dihydro-3H- dibenzo[de,h]cinnoline-3,7-dione derivatives, a novel group of anticancer agents active on a multidrug resistant cell line. Bioorganic Med Chem. 2002; 11: 561-72. https:// doi.org/10.1016/S0968-0896(02)00425-X. open in new tab
- Borowski E, Stefanska B, Dzieduszycka M, Cybulski M, Szelejewski W, Obukowicz J, Bontemps-Gracz MM, Wysocka M, Mazerski J, Punda P, Wietrzyk J. Asymmetrically substituted anthrapyridazone derivatives as cytostatics. United States: US Patent US 2014/0031357 A1; US Patent 2014/0031357 A1, 2014.
- Grandi M, Geroni C, Giuliani FC. Isolation and characterization of a human colon adenocarcinoma cell line resistant to doxorubicin. Br J Cancer [Internet]. 1986; 54: www.impactjournals.com/oncotarget 515-8. Available from http://www.pubmedcentral.nih.gov/ articlerender.fcgi?artid=2001636&tool=pmcentrez&rende rtype=abstract open in new tab
- Carrier F, Georgel PT, Pourquier P, Blake M, Kontny HU, Antinore MJ, Gariboldi M, Myers TG, Weinstein JN, Pommier Y, Fornace a J. Gadd45, a p53-responsive stress protein, modifies DNA accessibility on damaged chromatin. Mol Cell Biol. 1999; 19: 1673-85. open in new tab
- Siu FM, Pommier Y. Sequence selectivity of the cleavage sites induced by topoisomerase i inhibitors: A molecular dynamics study. Nucleic Acids Res. 2013; 41: 10010-9. https://doi.org/10.1093/nar/gkt791. open in new tab
- Lee KC, Bramley RL, Cowell IG, Jackson GH, Austin CA. Proteasomal inhibition potentiates drugs targeting DNA topoisomerase II. Biochem Pharmacol [Internet]. open in new tab
- Elsevier Inc.; 2016; 103: 29-39. https://doi.org/10.1016/j. bcp.2015.12.015. open in new tab
- Zhao H, Traganos F, Darzynkiewicz Z. Kinetics of histone H2AX phosphorylation and Chk2 activation in A549 cells treated with topotecan and mitoxantrone in relation to the cell cycle phase. Cytom Part A. 2008; 73: 480-9. https://doi. org/10.1002/cyto.a.20574. open in new tab
- Zhao H, Traganos F, Darzynkiewicz Z. Phosphorylation of p53 on Ser15 during cell cycle caused by Topo I and Topo II inhibitors in relation to ATM and Chk2 activation. Cell Cycle. 2008; 7: 3048-55. https://doi.org/10.4161/ cc.7.19.6750. open in new tab
- Zhao H, Rybak P, Dobrucki J, Traganos F, Darzynkiewicz Z. Relationship of DNA damage signaling to DNA replication following treatment with DNA topoisomerase inhibitors camptothecin/topotecan, mitoxantrone, or etoposide. Cytom Part A. 2012; 81 A: 45-51. https://doi.org/10.1002/ cyto.a.21172. open in new tab
- Rybak P, Hoang A, Bujnowicz L, Bernas T, Zarębski M, Darzynkiewicz Z, Dobrucki J. Low level phosphorylation of histone H2AX on serine 139 (γH2AX) is not associated with DNA double-strand breaks. 2016; 139. open in new tab
- Chen M-C, Pan S-L, Shi Q, Xiao Z, Lee K-H, Li T-K, Teng C-M. QS-ZYX-1-61 induces apoptosis through topoisomerase II in human non-small-cell lung cancer A549 cells. Cancer Sci [Internet]. 2012; 103: 80-7. https://doi. org/10.1111/j.1349-7006.2011.02103.x. open in new tab
- Kinner A, Wu W, Staudt C, Iliakis G. γ-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin. Nucleic Acids Res [Internet]. 2008; 36: 5678-94. https://doi.org/10.1093/nar/gkn550. open in new tab
- Huang X, Tanaka T, Kurose A, Traganos F, Darzynkiewicz Z. Constitutive histone H2AX phosphorylation on Ser-139 in cells untreated by genotoxic agents is cell-cycle phase specific and attenuated by scavenging reactive oxygen species. Int J Oncol. 2006; 29: 495-501. open in new tab
- Williams RS, Williams JS, Tainer JA. Mre11-Rad50-Nbs1 is a keystone complex connecting DNA repair machinery, double-strand break signaling, and the chromatin templateThis paper is one of a selection of papers published in this Special Issue, entitled 28th International West Coast Chromatin a. Biochem Cell Biol [Internet]. 2007; 85: 509- 20. https://doi.org/10.1139/O07-069. open in new tab
- Spencer DMS, Bilardi RA, Koch TH, Post GC, Nafie JW, Kimura KI, Cutts SM, Phillips DR. DNA repair in response to anthracycline-DNA adducts: A role for both homologous recombination and nucleotide excision repair. open in new tab
- Mutat Res. 2008; 638: 110-21. https://doi.org/10.1016/j. mrfmmm.2007.09.005. open in new tab
- Rocca CJ, Soares DG, Bouzid H, Henriques JAP, Larsen AK, Escargueil AE. BRCA2 is needed for both repair and cell cycle arrest in mammalian cells exposed to S23906, an anticancer monofunctional DNA binder. Cell Cycle. 2015; 14: 2080-90. https://doi.org/10.1080/15384101.20 15.1042632. open in new tab
- Soares DG, Escargueil AE, Poindessous V, Sarasin A, de Gramont A, Bonatto D, Henriques JAP, Larsen AK. Replication and homologous recombination repair regulate DNA double-strand break formation by the antitumor alkylator ecteinascidin 743. Proc Natl Acad Sci U S A [Internet]. 2007; 104: 13062-7. https://doi.org/10.1073/ pnas.0609877104. open in new tab
- Davis FM, Tsao TY, Fowler SK, Rao PN. Monoclonal antibodies to mitotic cells. Proc Natl Acad Sci U S A. 1983; 80: 2926-30. https://doi.org/10.1073/pnas.80.10.2926. open in new tab
- Gorenstein DG. Conformation and Dynamics of DNA and Protein-DNA Complexes by 31P NMR. Chem Rev [Internet]. 1994; 94: 1315-38. https://doi.org/10.1021/ cr00029a007. open in new tab
- Koepler O, Mazzini S, Bellucci MC, Mondelli R, Baro A, Laschat S, Hotfilder M, Viseur C, Frey W. Synthesis and DNA binding properties of novel benzo[b]isoquino[2,3- h]-naphthyridines. Org Biomol Chem [Internet]. 2005; 3: 2848-58. https://doi.org/10.1039/b503281d. open in new tab
- Mazzini S, Scaglioni L, Animati F, Mondelli R. Interaction between double helix DNA fragments and the new antitumor agent sabarubicin, Men10755. Bioorganic Med Chem [Internet]. open in new tab
- Elsevier Ltd; 2010; 18: 1497-506. https:// doi.org/10.1016/j.bmc.2010.01.012. open in new tab
- Mazzini S, Scaglioni L, Mondelli R, Caruso M, Sirtori FR. The interaction of nemorubicin metabolite PNU-159682 with DNA fragments d(CGTACG)2, d(CGATCG)2 and d(CGCGCG)2 shows a strong but reversible binding to G:C base pairs. Bioorganic Med Chem [Internet]. open in new tab
- Elsevier Ltd; 2012; 20: 6979-88. https://doi.org/10.1016/j. bmc.2012.10.033. open in new tab
- Mazzini S, Bellucci MC, Mondelli R. Mode of binding of the cytotoxic alkaloid berberine with the double helix oligonucleotide d(AAGAATTCTT)2. Bioorganic Med Chem. 2002; 11: 505-14. https://doi.org/10.1016/ S0968-0896(02)00466-2. open in new tab
- Mazzini S, Bellucci MC, Dallavalle S, Fraternali F, Mondelli R. Mode of binding of camptothecins to double www.impactjournals.com/oncotarget helix oligonucleotides. Org Biomol Chem. 2004; 2: 505-13. https://doi.org/10.1039/b312780j. open in new tab
- Rhodes D, Lipps HJ. G-quadruplexes and their regulatory roles in biology. Nucleic Acids Res [Internet]. 2015; 43: gkv862. https://doi.org/10.1093/nar/gkv862. open in new tab
- Kato Y, Ohyama T, Mita H, Yamamoto Y. Dynamics and Thermodynamics of Dimerization of Parallel G-Quadruplexed DNA Formed from d(TTAGn)(n = 3-5). J am. 2005; 127: 9980-1. open in new tab
- Capranico G, Zunino F, Kohn KW, Pommier Y. Sequence- selective topoisomerase II inhibition by anthracycline derivatives in SV40 DNA: Relationship with DNA binding affinity and cytotoxicity. Biochemistry. 1990; 29: 562-9. https://doi.org/10.1021/bi00454a033. open in new tab
- Dziegielewski J, Slusarski B, Konitz A, Skladanowski A, Konopa J. Intercalation of imidazoacridinones to DNA and its relevance to cytotoxic and antitumor activity. Biochem Pharmacol. 2002; 63: 1653-62. https://doi.org/10.1016/ S0006-2952(02)00916-4. open in new tab
- Parrino B, Carbone A, Ciancimino C, Spanò V, Montalbano A, Barraja P, Cirrincione G, Diana P, Sissi C, Palumbo M, Pinato O, Pennati M, Beretta G, et al. Water- soluble isoindolo[2,1-a]quinoxalin-6-imines: in vitro antiproliferative activity and molecular mechanism(s) of action. Eur J Med Chem. 2015; 94: 149-62. https://doi. org/10.1016/j.ejmech.2015.03.005. open in new tab
- Lemke K, Poindessous V, Skladanowski A, Larsen AK. The antitumor triazoloacridone C-1305 is a topoisomerase II poison with unusual properties. Mol Pharmacol. 2004; 66: 1035-42. https://doi.org/10.1124/mol.104.000703. open in new tab
- Vilenchik MM, Knudson AG. Endogenous DNA double- strand breaks: production, fidelity of repair, and induction of cancer. Proc Natl Acad Sci U S A. 2003; 100: 12871-6. https://doi.org/10.1073/pnas.2135498100. open in new tab
- Sabourin M, Osheroff N. Sensitivity of human type II topoisomerases to DNA damage: stimulation of enzyme- mediated DNA cleavage by abasic, oxidized and alkylated lesions. Nucleic Acids Res [Internet]. 2000; 28: 1947- 54. Available from http://www.pubmedcentral.nih.gov/ articlerender.fcgi?artid=103304&tool=pmcentrez&rendert ype=abstract open in new tab
- Staresincic L, Fagbemi AF, Enzlin JH, Gourdin AM, Wijgers N, Dunand-Sauthier I, Giglia-Mari G, Clarkson SG, Vermeulen W, Schärer OD. Coordination of dual incision and repair synthesis in human nucleotide excision repair. EMBO J [Internet]. 2009; 28: 1111-20. https://doi. org/10.1038/emboj.2009.49. open in new tab
- Winkler GS, Araújo SJ, Fiedler U, Vermeulen W, Coin F, Egly JM, Hoeijmakers JHJ, Wood RD, Timmers HTM, Weeda G. TFIIH with inactive XPD helicase functions in transcription initiation but is defective in DNA repair. J Biol Chem. 2000; 275: 4258-66. https://doi.org/10.1074/ jbc.275.6.4258. open in new tab
- Sarker AH, Tsutakawa SE, Kostek S, Ng C, Shin DS, Peris M, Campeau E, Tainer JA, Nogales E, Cooper PK. Recognition of RNA polymerase II and transcription bubbles by XPG, CSB, and TFIIH: Insights for transcription-coupled repair and Cockayne syndrome. Mol Cell. 2005; 20: 187-98. https://doi.org/10.1016/j. molcel.2005.09.022. open in new tab
- Kondo N, Takahashi A, Mori E, Noda T, Zdzienicka MZ, Thompson LH, Helleday T, Suzuki M, Kinashi Y, Masunaga S, Ono K, Hasegawa M, Ohnishi T. FANCD1/BRCA2 plays predominant role in the repair of dna damage induced by ACNU or TMZ. PLoS One. 2011; 6: 1-8. https://doi. org/10.1371/journal.pone.0019659. open in new tab
- Mao Z, Bozzella M, Seluanov A, Gorbunova V. DNA repair by nonhomologous end joining and homologous recombination during cell cycle in human cells. Cell Cycle [Internet]. 2008; 7: 2902-6. https://doi.org/10.2964/jsik. kuni0223. open in new tab
- Rybak P, Hoang A, Bujnowicz L, Bernas T, Zarębski M, Darzynkiewicz Z, Dobrucki J. Low level phosphorylation of histone H2AX on serine 139 (γH2AX) is not associated with DNA double-strand breaks. Oncotarget. 2016; 139. open in new tab
- Rao JY, Li N. Microfilament Actin Remodeling as a Potential Target for Cancer Drug Development. Curr Cancer Drug Targets. 2004; 4: 345-54. https://doi. org/10.2174/1568009043332998. open in new tab
- Trendowski M, Wong V, Wellington K, Hatfield S, Fondy TP. Tolerated doses in zebrafish of cytochalasins and jasplakinolide for comparison with tolerated doses in mice in the evaluation of pre-clinical activity of microfilament- directed agents in tumor model systems in vivo. In Vivo (Brooklyn). 2014; 28: 1021-32. open in new tab
- Gewirtz DA. A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem Pharmacol. 1999; 57: 727-41. https://doi. org/10.1016/S0006-2952(98)00307-4. open in new tab
- Larsen AK, Skladanowski A. Perturbations of Cellular Functions by Topoisomerase II Inhibitors" All Roads Lead to Cell Death? In: Gewirtz D a., Holt S, Grant S, editors. Cancer Drug Discovery and Development. Totowa, New Jersey 07512: Humana Press; 2007. p. 407-22. open in new tab
- Scaglioni L, Mondelli R, Artali R, Ric-cardi Sirtori F, Mazzini S, Riccardi Sirtori F. Nemorubicin and doxorubicin bind the G-quadruplex sequences of the human telomeres and of the c-MYC promoter element Pu22. BBA -Gen Subj [Internet]. open in new tab
- Elsevier B.V.; 2016; 1860: 1129-38. https://doi. org/10.1016/j.bbagen.2016.02.011. open in new tab
- Poruchynsky MS, Komlodi-Pasztor E, Trostel S, Wilkerson J, Regairaz M, Pommier Y, Zhang X, Kumar Maity T, Robey R, Burotto M, Sackett D, Guha U, Fojo AT. Microtubule-targeting agents augment the toxicity of DNA- damaging agents by disrupting intracellular trafficking of www.impactjournals.com/oncotarget DNA repair proteins. Proc Natl Acad Sci [Internet]. 2015; 112: 1571-6. https://doi.org/10.1073/pnas.1416418112. open in new tab
- Nitiss JL, Soans E, Rogojina A, Seth A, Mishina M. Topoisomerase Assays. Curr Protoc Pharmacol. 2012. 789- 802 p. https://doi.org/10.1002/0471141755.ph0303s57. Topoisomerase. open in new tab
- Morris KF, Johnson Jr CS. Diffusion-ordered two- dimensional nuclear magnetic resonance spectroscopy. open in new tab
- J Am Chem Soc [Internet]. 1992; : 3139-41. https://doi. org/10.1021/ja00034a071. open in new tab
- Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B, Tinevez J-Y, White DJ, Hartenstein V, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods [Internet]. 2012; 9: 676-82. https:// doi.org/10.1038/nmeth.2019. open in new tab
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