THE EPIGENETIC PROTECTION SHELL OF EUCHROMATIN DNA E-Book

Andreas Johannes Kesel

• Herausgeber: tredition
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 191

Veröffentlichungsjahr: 2023

Beschreibung

Oxygen exists in two gaseous (dioxygen and ozone) and six solid allotropic modifications. An additional allotropic modification of oxygen, the cyclooctaoxygen, was predicted to exist in 1990. The first synthesis and characterization of cyclooctaoxygen as its sodium crown complex, isolated in the form of three cytosine nucleoside hydrochloride complexes, was reported in 2016. Cyclooctaoxygen sodium was synthesized in vitro from atmospheric oxygen, or catalase effect-generated oxygen, under catalysis of cytosine nucleosides and either ninhydrin or eukaryotic low-molecular weight RNA. Thin-layer chromatographic mobility shift assays were applied on specific nucleic acids and the cyclooctaoxygen sodium complex. The cationic cyclooctaoxygen sodium complex was shown to bind to nucleic acids (RNA and DNA), to associate with single-stranded DNA and spermine phosphate, and to be essentially non-toxic to cultured mammalian cells at 0.1–1.0 mM concentration. It is postulated that cyclooctaoxygen is formed in most eukaryotic cells in vivo from dihydrogen peroxide in a catalase reaction catalysed by cytidine and RNA. A molecular biological model was deduced for a first epigenetic shell of eukaryotic in vivo DNA. This model incorporates an epigenetic explanation for the interactions of the essential micronutrient selenium (as selenite) with eukaryotic in vivo DNA. The sperminium hydrogen phosphate/cyclooctaoxygen sodium complex is calculated to cover the actively transcribed regions (2.6%) of bovine lymphocyte interphase genome. Cyclooctaoxygen seems to be naturally absent in hypoxia-induced highly condensed chromatin, taken as a model for eukaryotic metaphase/anaphase/early telophase mitotic chromatin. Hence, it is proposed that the cyclooctaoxygen sodium-bridged sperminium hydrogen phosphate and selenite coverage serves as an epigenetic shell of actively transcribed gene regions in eukaryotic 'open' euchromatin DNA. It is proposed that the sperminium phosphate/cyclooctaoxygen sodium complex coverage of nucleic acids is essential to eukaryotic gene regulation and promoted proto-eukaryotic evolution. Cyclooctaoxygen sodium-bridged sperminium hydrogen selenite is calculated to serve as a marker shell component at ATG start codons in human euchromatin DNA mRNA genes, both at the translation initiation triplet and at 5′-untranslated region upstream ATGs. The total herbicide glyphosate (ROUNDUP®) and its metabolite (aminomethyl)phosphonic acid (AMPA) are proved to represent 'epigenetic poisons', since they both selectively destroy the cyclooctaoxygen sodium complex. This definition is of reason, since the destruction of cyclooctaoxygen is certainly sufficient to bring the protection shield of human euchromatin into collateral epigenetic collapse. The total herbicide glyphosate and its environmental metabolite (aminomethyl)phosphonic acid (AMPA) can be associated in vitro with catalytic detoriation of eukaryotic euchromatin genetic information. The epigenetic shell of eukaryotic euchromatin is susceptible to decay induced by catalytic epigenetic poisons threatening eukaryotic genomic heritage.

Leseprobe

ANDREAS J. KESEL

THE EPIGENETIC PROTECTION SHELL OF EUCHROMATIN DNA

SELENIUM CONTENTDETORIATION BY GLYPHOSATE

© 2023 Andreas Johannes Kesel

ISBN Hardcover: 978-3-347-94444-2

ISBN E-Book: 978-3-347-94445-9

Druck und Distribution im Auftrag des Autors:

tredition GmbH, Heinz-Beusen-Stieg 5, 22926 Ahrensburg, Germany

Das Werk, einschließlich seiner Teile, ist urheberrechtlich geschützt. Für die Inhalte ist der Autor verantwortlich. Jede Verwertung ist ohne Zustimmung des Autors unzulässig. Die Publikation und Verbreitung erfolgen im Auftrag des Autors, zu erreichen unter: tredition GmbH, Abteilung "Impressumservice", Heinz-Beusen-Stieg 5, 22926 Ahrensburg, Deutschland.

Table of Contents

Cover

Title Page

Copyright

Biography of the Author

Publications of the Author

Patents of the Author

Acknowledgements

Dedication

Preface and Abstract

Introduction

References

Chapter One: Cyclooctaoxygen

1. Cyclooctaoxygen as its Sodium Complex

1.1. Introduction

1.2. Synthesis and characterization of NC

1.3. Synthesis and characterization of dNC

1.4. Catalase assay with NC and Candida utilis RNA

1.5. Synthesis and characterization of RC

1.6. Electrospray ionization mass spectrometry of RC

2. References

Chapter Two: Cyclooctaoxygen Sodium Complex

1. Biochemical Affinities and Properties of Cyclooctaoxygen Sodium

1.1. Binding of NC to Candida utilis RNA

1.2. Binding of NC to salmon testes single-stranded DNA and spermine phosphate

1.3. In vitro biological effects of NC and dNC on cultured mammalian cells

2. Color Reaction of Cyclooctaoxygen Sodium

2.1. Color assay for cyclo-O8-Na+ contained in RC – destruction of cyclo-O8-Na+ by the glyphosate metabolite (aminomethyl)phosphonic acid

2.2. Color assay for cyclo-O8-Na+ contained in RC – destruction of cyclo-O8-Na+ by glyphosate and ROUNDUP®

3. Enzymatic investigations with the glyphosate metabolite (aminomethyl)phosphonic acid (AMPA)

4. References

Chapter Three: Euchromatin Protection Shell

1. The Epigenetic Protection Shell of Eukaryotic Euchromatin

1.1. A molecular model for an epigenetic protection shell of eukaryotic euchromatin DNA

1.2. Calculation of the genomic coverage by the cyclooctaoxygen sodium-bridged spermine phosphate epigenetic shell of interphase DNA in bovine lymphocytes

1.3. Calculation of the spermine coverage of highly condensed mitotic metaphase DNA in HeLa S3 cells

1.4. Calculation of the polyamine coverage of maximally condensed mitotic late anaphase/early telophase DNA in murine cryptal enterocytes

2. The Selenium Content of the Epigenetic Protection Shell of Eukaryotic Euchromatin

2.1. Calculation of the hydrogen selenite (HSeO3–) coverage of human euchromatin DNA specifically at ATG start codon sequences

2.2. Implications for the selenium content of the euchromatin protection shell

3. Calculation of the Apparent Acid Dissociation Constant of the Human Genome DNA, and the Intranuclear Micro-pH Mediated by Single Spermine Occupation, in Comparison to Spermine Phosphate/Cyclooctaoxygen Sodium Complex Occupation, of Human Interphase Euchromatin

4. References

Chapter Four: Implications for the Euchromatic Protection Shell

1. The Destruction of the Euchromatic Protection Shell by Common DNA Isolation Methods

2. Implications for the Euchromatic Protection Shell

2.1. The genetic code and the euchromatic protection shell

2.2. Chromatin condensation under hypoxia

2.3. Implications for the euchromatic protection shell

3. The Euchromatic Protection Shell and Glyphosate

4. The Evolutionary Significance of the Euchromatic Protection Shell

5. References

Appendix: Materials and Methods, Chemical Synthesis, Experimental Instructions, Genomic Calculations and Supplementary Data

1. Materials and Methods

1.1. Materials

1.2. Methods

1.3. Software

1.4. Photographing

2. Chemical Synthesis

2.1. Cytidine hydrochloride

2.2. Cytidine hydrochloride – aqua(chloro)(octoxocane-κ4O1,O3,O5,O7)sodium (4:1) monohydrate hemiacetonate (NC)

2.3. 2′-Deoxycytidine hydrochloride – aqua(chloro)(octoxocane-κ4O1,O3,O5,O7)sodium (2:1) dihydrate (dNC)

2.4. Cytidine hydrochloride – µ-chloro(µ-hydroxy)bis(octoxocane-κ4O1,O3,O5,O7)disodium (1:2) hemi(hemi)acetonate (RC)

3. Experimental Instructions

3.1. Catalase effect assays

3.2. Binding of NC to C. utilis low-molecular weight RNA

3.3. Binding of NC to salmon testes ssDNA

3.4. Binding of NC to salmon testes ssDNA in presence of spermine X 1 ⅓ (sodium dihydrogen phosphate) × 9 H2O

3.5. Cytotoxicity and HIV-1LAI replication reverse transcriptase assays

3.6. Cytotoxicity and HBV ayw antiviral assays

3.7. Cytotoxicity and influenza A virus replication antiviral assays

3.8. Cytotoxicity and chikungunya virus replication antiviral assays

3.9. Cytotoxicity and MERS coronavirus replication antiviral assays

3.10. Neutral red assay

3.11. Virus yield reduction assay

3.12. Color assay for cyclo-O8-Na+ contained in RC – destruction of cyclo-O8-Na+ by the glyphosate metabolite (aminomethyl)phosphonic acid

3.13. Control color assay for potential reduction of elemental iodine by the glyphosate metabolite (aminomethyl)phosphonic acid

3.14. Color assay for cyclo-O8-Na+ contained in RC – destruction of cyclo-O8-Na+ by glyphosate and ROUNDUP®

3.15. Enzyme assay of the glyphosate metabolite (aminomethyl)phosphonic acid with human mitochondrial γ-aminobutyric acid transaminase

3.16. Enzyme assay of the glyphosate metabolite (aminomethyl)phosphonic acid with human wild-type alanine: glyoxylate aminotransferase

4. Genomic Calculations

4.1. Calculation of the genomic coverage by the cyclooctaoxygen sodium-bridged spermine phosphate epigenetic shell of interphase DNA in bovine lymphocytes

4.2. Calculation of the spermine coverage of highly condensed mitotic metaphase DNA in HeLa S3 cells

4.3. Calculation of the polyamine coverage of maximally condensed mitotic late anaphase/early telophase DNA in murine cryptal enterocytes

4.4. Calculation of the hydrogen selenite (HSeO3–) coverage of human euchromatin DNA specifically at ATG start codon sequences

4.5. Calculation of the apparent acid dissociation constant of the human genome DNA

4.6. Calculation of the hypothetical intranuclear micro-pH mediated by single spermine occupation of human interphase euchromatin

4.7. Calculation of the theoretical intranuclear micro-pH mediated by sperminium hydrogen phosphate/cyclooctaoxygen sodium complex occupation of human interphase euchromatin

5. Supplementary Data

5.1. Table of contents

5.2. Supplementary References

5.2. Supplementary References

THE EPIGENETIC PROTECTION SHELL OF EUCHROMATIN DNA

Cover

Title Page

Copyright

Biography of the Author

Appendix: Materials and Methods, Chemical Synthesis, Experimental Instructions, Genomic Calculations and Supplementary Data

THE EPIGENETIC PROTECTION SHELL OF EUCHROMATIN DNA

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BIOGRAPHY OF THE AUTHOR

1990 ABITUR. 1991–1993 CHEMISTRY SCHOOL DR. ERWIN ELHARDT, STUDY OF CHEMICAL-TECHNICAL ASSISTANT (CTA). 1993 PRACTICAL TRAINING, MAX-PLANCK-INSTITUTE FOR BIOCHEMISTRY, MARTINSRIED, GERMANY, DEPARTMENT OF PROTEIN CHEMISTRY OF DR. FRIEDRICH LOTTSPEICH, IN THE FORMER LABORATORY OF DR. PEHR VICTOR EDMAN (ADVISOR: KERSTIN ANDERSSON, GENERAL TRAINING IN PROTEIN CHEMISTRY, ELECTROPHORESIS, AND PROTEIN SEQUENCING BY THEEDMAN METHOD). 1993 PRACTICAL TRAINING, MAX-PLANCK-INSTITUTE FOR NEUROBIOLOGY, MARTINSRIED, GERMANY, DEPARTMENT OF NEUROIMMUNOLOGY OF PROF. DR. DR. H.C. HARTMUT WEKERLE (ADVISOR: DR. ANTONIO IGLESIAS, TRAINING IN MOLECULAR BIOLOGY AND DNA SEQUENCING). 1993–1995 WORK AS CHEMICAL-TECHNICAL ASSISTANT AT MAX-PLANCK-INSTITUTE FOR BIOCHEMISTRY IN THE DEPARTMENTOF VIRUS RESEARCH OF PROF. DR. DR. DR. H.C. PETER HANS HOFSCHNEIDER, WITH SPECIAL TRAINING IN THE MOLECULAR BIOLOGY OF HUMAN HEPATITIS B VIRUS. 1995–2000 STUDY OF PHARMACY AT LUDWIG-MAXIMILIANS-UNIVERSITY, MUNICH, GERMANY. 2004–2005 STUDY OF PHARMACY AT JULIUS-MAXIMILIANS UNIVERSITY OF WÜRZBURG, GERMANY. 2006–2011 DOCTORAL STUDY AT JULIUS-MAXIMILIANS UNIVERSITY OF WÜRZBURG, GERMANY, IN THE DEPARTMENT OF PHARMACEUTICAL CHEMISTRY OF PROF. DR. ULRIKE HOLZGRABE. 2011–2015 PUBLICATION WORK AS PRIVATE RESEARCHER IN MUNICH, GERMANY. 2015–2017 WORK AS CHIEF MEDICINAL CHEMIST FOR POP TEST ONCOLOGY LLC OF RANDICE LISA ALTSCHUL, CLIFFSIDE PARK, NJ, USA. 1998 ELECTION AS AN EXTERNAL MEMBER OF THE NEW YORK ACADEMY OF SCIENCES, NEW YORK, USA. 2005 MEMBER OF THE AMERICAN CHEMICAL SOCIETY, DIVISION OF MEDICINAL CHEMISTRY. 18 PUBLICATIONS AND/OR CONGRESS ABSTRACTS IN PEER-REVIEWED JOURNALS. 2 BOOKS PUBLISHED. 30 CO-AUTHORED PATENTS.

PUBLICATIONS OF THE AUTHOR

[1] Eberhard Hildt, Stephan Urban, Andreas Kesel, Peter Hans Hofschneider. Functional characterization of baculovirus-derived MHBst, Molecular Biology of Hepatitis B Viruses, October 3–6 1994, Institut Pasteur, Paris, France (Chair: Marie Annick Buendia, Alan McLachlan).

[2] Stephan Urban, Eberhard Hildt, Christoph Eckerskorn, Andreas Kesel, Peter Hans Hofschneider. Mass Spectrometric Analysis of Baculovirus-Derived HBX, Molecular Biology of Hepatitis B Viruses, October 3–6 1994, Institut Pasteur, Paris, France (Chair: Marie Annick Buendia, Alan McLachlan).

[3] Andreas J. Kesel, Stephan Urban, Walter Oberthür. Interconvertible (Z/E)-Stereoisomers of a Vitamin B6 Coenzyme Analog Derived from Pyridoxal 5′-Phosphate and Rhodanine, Tetrahedron 1996, 52, 14787–14800.

[4] Andreas J. Kesel, Isolde Sonnenbichler, Kurt Polborn, Lutz Gürtler, Wolfgang E. F. Klinkert, Manuel Modolell, Andreas K. Nüssler, Walter Oberthür. A New Antioxidative Vitamin B6 Analogue Modulates Pathophysiological Cell Proliferation and Damage, Bioorg. Med. Chem. 1999, 7, 359–367.

[5] Andreas J. Kesel. A System of Protein Target Sequences for Anti-RNA-viral Chemotherapy by a Vitamin B6-Derived Zinc-Chelating Trioxa-adamantane-triol, Bioorg. Med. Chem. 2003, 11, 4599–4613.

[6] Andreas J. Kesel. Synthesis of retinoid vitamin A–vitamin B6 conjugate analogues for antiviral chemotherapy, Biochem. Biophys. Res. Commun. 2003, 300, 793–799.

[7] Julian A. Tanner, Bo-Jian Zheng, Jie Zhou, Rory M. Watt, Jie-Qing Jiang, Kin-Ling Wong, Yong-Ping Lin, Lin-Yu Lu, Ming-Liang He, Hsiang-Fu Kung, Andreas J. Kesel, Jian-Dong Huang. The Adamantane-Derived Bananins Are Potent Inhibitors of the Helicase Activities and Replication of SARS Coronavirus, Chem. Biol. (Cell Chem. Biol.) 2005, 12, 303–311.

[8] Andreas J. Kesel. Synthesis of Novel Test Compounds for Antiviral Chemotherapy of Severe Acute Respiratory Syndrome (SARS), Curr. Med. Chem. 2005, 12, 2095–2162.

[9] Andreas J. Kesel. The Bananins: New Anticorona-RNA-Viral Agents with Unique Structural Signature, Anti-Infective Agents Med. Chem. 2006, 5, 161–174.

[10] Andreas J. Kesel. Broad-spectrum antiviral activity including human immunodeficiency and hepatitis C viruses mediated by a novel retinoid thiosemicarbazone derivative, Eur. J. Med. Chem. 2011, 46, 1656–1664.

[11] Andreas J. Kesel. An Update on the Bananins: Anti-RNA-Viral Agents with Unique Structural Signature, Anti-Infective Agents 2013, 11, 1–21.

[12] Andreas J. Kesel, Hans-Christoph Weiss, Andreas Schönleber, Craig W. Day, Dale L. Barnard, Mervi A. Detorio, Raymond F. Schinazi. Antiviral agents derived from novel 1-adamantyl singlet nitrenes, Antivir. Chem. Chemother. 2013, 23, 113–128.

[13] Andreas J. Kesel, Zhuhui Huang, Michael G. Murray, Mark N. Prichard, Laura Caboni, Daniel K. Nevin, Darren Fayne, David G. Lloyd, Mervi A. Detorio, Raymond F. Schinazi. Retinazone inhibits certain blood-borne human viruses including Ebola virus Zaire, Antivir. Chem. Chemother. 2014, 23, 197–215.

[14] Andreas Schönleber, Sander van Smaalen, Hans-Christoph Weiss, Andreas J. Kesel. N—H · O and C—H · F hydrogen bonds in the incommensurately modulated crystal structure of adamantan-1-ammonium4-fluorobenzoate, Acta Crystallogr. B Struct. Sci. Cryst. Eng. Mater. 2014, 70, 652–659.

[15] Francesco Saettini, Matteo F. Olivieri, Andreas J. Kesel, Laura Bonalume, Francesca Marzari. Dermatology in ancient Greece: The myth of Melampus and the use of Helleborus, Vth Congresso Nazionale SiDerP (Società Italiana di Dermatologia Pediatrica – Italian Society of Pediatric Dermatology), April 16–18 2015, Florio Park Hotel, Palermo, Italy.

[16] Andreas J. Kesel, Craig W. Day, Catherine M. Montero, Raymond F. Schinazi. A new oxygen modification cyclooctaoxygen binds to nucleic acids as sodium crown complex, Biochim. Biophys. Acta 2016, 1860, 785–794.

[17] Matteo F. Olivieri, Francesca Marzari, Andreas J. Kesel, Laura Bonalume, Francesco Saettini. Pharmacology and psychiatry at the origins of Greek medicine: The myth of Melampus and the madness of the Proetides, J. Hist. Neurosci. 2017, 26, 193–215.

[18] Andreas J. Kesel. The Spermine Phosphate-Bound Cyclooctaoxygen Sodium Epigenetic Shell of Euchromatin DNA Is Destroyed by the Epigenetic Poison Glyphosate, Preprints 2017, 2017010086, https://doi.org/10.20944/preprints201701.0086.v4.

[19] Andreas J. Kesel. The Spermine Phosphate-Bound Cyclooctaoxygen Sodium Epigenetic Shell of Euchromatin DNA Is Destroyed by the Epigenetic Poison Glyphosate, Arch. Clin. Biomed. Res. 2023, 7, 171–190, https://doi.org/10.26502/acbr.50170331.

[20] Andreas J. Kesel. The Potential Healing of Cancer with P53 (Re)Activators. Two New Drugs Exploiting Cancer′s Warburg Effect, 1st ed., tredition GmbH, Ahrensburg, Germany, 2023, ISBN 978-3384003126.

PATENTS OF THE AUTHOR

[1] Andreas J. Kesel, Walter Oberthür. (Z)-5-[[3-Hydroxy-2-methyl-5-[(phosphonooxy)methyl]-4-pyridinyl]methylen]-2-thioxo-4-thiazolidinon, Verfahren zu dessen Herstellung und Verwendung. Ger. Pat. DE 196 45 974 C1 (1998). Filed 1996/11/07.

[2] Andreas J. Kesel, Walter Oberthür. Mono-, oligo-, and polymeric Knoevenagel condensation products useful e.g. in pharmaceuticals, cosmetics and assay procedures. Ger. Pat. DE 198 19 820 A1 (2000). Filed 1998/05/04.

[3] Andreas J. Kesel, Walter Oberthür. NEW KNOEVENAGEL CONDENSATION PRODUCTS, METHOD FOR THEIR PRODUCTION AND THEIR USE. PCT/WIPO Pat. Appl. WO/1998/020013 A1 (1998). Filed 1997/11/07.

[4] Andreas J. Kesel, Walter Oberthür. NEW KNOEVENAGEL CONDENSATION PRODUCTS, METHOD FOR THEIR PRODUCTION AND THEIR USE. Eur. Pat. Appl. EP 0 937 089 A1 (1999). Filed 1997/11/07.

[5] Andreas J. Kesel, Walter Oberthür. MONOMERIC, OLIGOMERIC AND POLYMERIC KNOEVENAGEL CONDENSATION PRODUCTS. PCT/WIPO Pat. Appl. WO/1999/057124 A1 (1999). Filed 1999/04/30.

[6] Walter Oberthür, Andreas J. Kesel. ANTIOXIDATIVE VITAMIN B6 ANALOGS. PCT/WIPO Pat. Appl. WO/2000/066599 A1 (2000). Filed 2000/04/28.

[7] Andreas J. Kesel, Walter Oberthür. MONOMERIC, OLIGOMERIC AND POLYMERIC KNOEVENAGEL CONDENSATION PRODUCTS. Eur. Pat. Appl. EP 1 075 481 A1 (2001). Filed 1999/04/30.

[8] Walter Oberthür, Andreas J. Kesel. NEW ANTIOXIDATIVE VITAMIN B6 ANALOGS. Eur. Pat. Appl. EP 1 173 451 A1 (2002). Filed 2000/04/28.

[9] Walter Oberthür, Andreas J. Kesel. Antioxidative vitamin B6 analogs. U.S. Pat. Appl. 6,369,042 B1 (2002). Filed 1999/11/10.

[10] Randice L. Altschul, Neil D. Theise, Andreas J. Kesel, Myron Rapkin, Rebecca O'Brien, Anthony R. Arment. PHARMACEUTICAL COMPOSITIONS AND METHODS. PCT/WIPO Pat. Appl. WO/2017/023694 A1 (2017). Filed 2016/07/28.

[11] Randice L. Altschul, Neil D. Theise, Andreas J. Kesel, Myron Rapkin, Rebecca O'Brien, Anthony R. Arment. PHARMACEUTICAL COMPOSITIONS AND METHODS. U.S. Pat. Appl. US 2017/0051007 A1 (2017). Filed 2016/07/28.

[12] Randice L. Altschul, Neil D. Theise, Andreas J. Kesel, Myron Rapkin, Rebecca O'Brien, Anthony R. Arment. PHARMACEUTICAL COMPOSITIONS AND METHODS. U.S. Pat. Appl. US 9,598,459 B2 (2017). Filed 2016/07/28.

[13] Randice L. Altschul, Neil D. Theise, Andreas J. Kesel, Myron Rapkin, Rebecca O'Brien, Anthony R. Arment. PHARMACEUTICAL COMPOSITIONS AND METHODS. U.S. Pat. Appl. US 2017/0128465 A1 (2017). Filed 2016/12/06.

[14] Randice L. Altschul, Neil D. Theise, Andreas J. Kesel, Myron Rapkin, Rebecca O'Brien, Anthony R. Arment. PHARMACEUTICAL COMPOSITIONS AND METHODS. U.S. Pat. Appl. US 9,855,284 B2 (2018). Filed 2016/12/06.

[15] Randice L. Altschul, Neil D. Theise, Andreas J. Kesel, Myron Rapkin, Rebecca O'Brien, Anthony R. Arment. THERAPEUTIC AGENTS AND METHODS:. PCT/WIPO Pat. Appl. WO/2018/067520 A2 (2018). Filed 2017/10/03.

[16] Randice L. Altschul, Neil D. Theise, Andreas J. Kesel, Myron Rapkin, Rebecca O'Brien, Anthony R. Arment. Pharmaceutical Compositions and Methods. U.S. Pat. Appl. US 2018/0185392 A1 (2018). Filed 2017/11/29.

[17] Randice L. Altschul, Neil D. Theise, Andreas J. Kesel, Myron Rapkin, Rebecca O'Brien, Anthony R. Arment. Pharmaceutical Compositions and Methods. Eur. Pat. Appl. EP 3 400 233 A1 (2018). Filed 2016/07/28.

[18] Randice L. Altschul, Neil D. Theise, Andreas J. Kesel, Myron Rapkin, Rebecca O'Brien, Anthony R. Arment. PHARMACEUTICAL COMPOSITIONS AND METHODS. U.S. Pat. Appl. US 10,238,666 B2 (2019). Filed 2017/11/29.

[19] Randice L. Altschul, Neil D. Theise, Andreas J. Kesel, Myron Rapkin, Rebecca O'Brien, Anthony Arment. PHARMACEUTICAL COMPOSITIONS AND METHODS. U.S. Pat. Appl. 2019/0134062 A1 (2019). Filed 2019/01/08.

[20] Randice L. Altschul, Neil D. Theise, Andreas J. Kesel, Myron Rapkin, Rebecca O'Brien, Anthony R. Arment. THERAPEUTIC AGENTS AND METHODS. Eur. Pat. Appl. EP 3 534 910 A2 (2019). Filed 2017/10/03.

[21] Randice L. Altschul, Neil D. Theise, Andreas J. Kesel, Myron Rapkin, Rebecca O'Brien, Anthony R. Arment. THERAPEUTIC AGENTS AND METHODS:. U.S. Pat. Appl. 2019/0381038 A1 (2019). Filed 2017/10/03.

[22] Randice L. Altschul, Neil D. Theise, Andreas J. Kesel, Myron Rapkin, Rebecca O'Brien, Anthony Arment. PHARMACEUTICAL COMPOSITIONS AND METHODS. U.S. Pat. Appl. US 10,517,881 B2 (2019). Filed 2019/01/08.

[23] Randice L. Altschul, Neil D. Theise, Andreas J. Kesel, Myron Rapkin, Rebecca O'Brien, Anthony Arment. PHARMACEUTICAL COMPOSITIONS AND METHODS. U.S. Pat. Appl. 2020/0101087 A1 (2020). Filed 2019/11/21.

[24] Randice L. Altschul, Neil D. Theise, Andreas J. Kesel, Myron Rapkin, Rebecca O'Brien, Anthony R. Arment. THERAPEUTIC AGENTS AND METHODS. U.S. Pat. Appl. US 11,040,037 B2 (2021). Filed 2017/10/03.

[25] Randice L. Altschul, Neil D. Theise, Andreas J. Kesel, Myron Rapkin, Rebecca O'Brien, Anthony R. Arment. THERAPEUTIC AGENTS AND METHODS. U.S. Pat. Appl. 2021/0353623 A1 (2021). Filed 2021/04/28.

[26] Randice L. Altschul, Neil D. Theise, Andreas J. Kesel, Myron Rapkin, Rebecca O'Brien, Anthony R. Arment. THERAPEUTIC AGENTS AND METHODS. U.S. Pat. Appl. US 11,224,599 B2 (2022). Filed 2021/04/28.

[27] Randice L. Altschul, Neil D. Theise, Andreas J. Kesel, Myron Rapkin, Rebecca O'Brien, Anthony R. Arment. THERAPEUTIC AGENTS AND METHODS. U.S. Pat. Appl. 2022/0298203 A1 (2022). Filed 2021/11/22.

[28] Randice L. Altschul, Neil D. Theise, Andreas J. Kesel, Myron Rapkin, Rebecca O'Brien, Anthony Arment. PHARMACEUTICAL COMPOSITIONS AND METHODS. U.S. Pat. Appl. US 11,576,921 B2 (2023). Filed 2019/11/21.

[29] Randice L. Altschul, Neil D. Theise, Andreas J. Kesel, Myron Rapkin, Rebecca O'Brien, Anthony Arment. PHARMACEUTICAL COMPOSITIONS AND METHODS. U.S. Pat. Appl. 2023/0142627 A1 (2023). Filed 2022/10/31.

[30] Randice L. Altschul, Neil D. Theise, Andreas J. Kesel, Myron Rapkin, Rebecca O'Brien, Anthony R. Arment. THERAPEUTIC AGENTS AND METHODS. U.S. Pat. Appl. 11,702,443 B2 (2023). Filed 2021/11/22.

ACKNOWLEDGEMENTS

The author wants to heartily thank R.F. Schinazi [Center for AIDS Research (now: Center for ViroScience and Cure), Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA, and (up to 2016) the Veterans Affairs Medical Center, Decatur, GA, USA, and Children’s Healthcare of Atlanta, Atlanta, GA, USA] and C.M. Montero (Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA) for the HIV-1LAI and HBV testings. In addition, the author heartily thanks C.W. Day (Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Science, Logan, Utah State University, Logan, UT, USA) for the influenza A, chikungunya and Middle East respiratory syndrome virus testings. The author is deeply indepted to T. Westfeld, E.-M. May, D. Wiegel, W. Wübbolt, O. Meier, R. Sachs, A. Karbach, W. Bergmeier, J. Moldenhauer and H.-J. Hühn (Currenta GmbH & Co. OHG, Leverkusen, Germany) for analytical services. I heartily thank H.J. Jodl for helpful discussions, E.A. Struys (Metabolic Unit, Department of Clinical Chemistry, University Hospital Vrije Universiteit, Amsterdam, The Netherlands) for performing the ABAT assays, and B. Cellini (Department of Medicine and Surgery, Physiology and Biochemistry Section, University of Perugia, Perugia, Italy, and Dipartimento di Neuroscienze, Biomedicina e Movimento, Sezione di Chimica Biologica, Università degli Studi di Verona, Verona, Italy) for conducting the AGT assays. I am obliged to K. Hecker, K. Meuser and K. Hecker (HEKAtech GmbH, Wegberg, Germany) for expert elemental analyses.

DEDICATION

THE AUTHOR DEDICATES THIS BOOK TO HIS LATE FATHER DR. RER. NAT. GÜNTHER KESEL AND TO HIS LOVELY MOTHER HILDEGARD FRIEDA FRANZISKA KESEL, WITHOUT THEIR SUPPORT THE AUTHOR'S WORK WOULD NOT HAVE BEEN POSSIBLE. THIS BOOK IS ALSO DEDICATED TO THE AUTHOR'S SOULMATE FARKAS GYÖNGYI, THE PEARL OF THE WOLF.

PREFACE AND ABSTRACT

This book is based on the publications:

[1] Andreas J. Kesel, Craig W. Day, Catherine M. Montero, Raymond F. Schinazi. A new oxygen modification cyclooctaoxygen binds to nucleic acids as sodium crown complex, Biochim. Biophys. Acta 2016, 1860, 785–794.

[2] Andreas J. Kesel. The Spermine Phosphate-Bound Cyclooctaoxygen Sodium Epigenetic Shell of Euchromatin DNA Is Destroyed by the Epigenetic Poison Glyphosate, Arch. Clin. Biomed. Res. 2023, 7, 171–190, https://doi.org/10.26502/acbr.50170331.