Design, synthesis and evaluation of light-activatable organic molecules that target-selectively degrade dna, proteins and carbohydrates; An interdisciplinary challenge for a synthetic organic chemist

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Abstract

We developed chemical methods for target-selective photodegradation of various biomacromolecules, including DNA, proteins, and carbohydrates. The DNA intercalator-carbohydrate moiety, without the enediyne structure found in the enediyne antibiotic neocarzinostatin chromophore, selectively degrades duplex DNA at guanine (G) nucleotides upon photoirradiation. Based on this finding, we designed and synthesized several artificial DNA intercalator-carbohydrate hybrids that can be photoactivated. Among them, several quinoxaline-carbohydrate hybrids were found to photodegrade duplex DNA at the G on the 5 side of 5-GG-3 sites. For protein degradation, we designed and synthesized several 2-phenylquinoline-steroid hormone hybrids and a porphyrin derivative, both of which selectively photodegrade the transcription factor estrogen receptor-α. In addition, we designed and synthesized fullerene-sugar and fullerene-sulfonic acid hybrids that selectively photodegrade HIV-1 protease and amyloid β, respectively. For carbohydrate degradation, we designed and synthesized anthraquinone-lectin hybrids and anthraquinone- and fullerene-boronic acid hybrids for selective photodegradation of target oligosaccharides having affinity for the lectin or boronic acid moiety of the hybrids. Furthermore, we successfully demonstrated practical uses for these light-activatable and molecular-targeted (LAMTA) molecules for controlling the function of DNA, proteins, and carbohydrates both in glass vessels and in cells. 1 Introduction 2 DNA Photodegrading Organic Molecules 2.1 DNA Intercalator-Carbohydrate Hybrids 2.2 Neocarzinostatin DNA Intercalator- Carbohydrate Hybrids for DNA Photodegradation 2.3 Quinoxaline-Carbohydrate Hybrids for DNA Photodegradation 3 Protein Photodegrading Organic Molecules 3.1 Quinoline-Steroid Hormone Hybrids for ER-α Photodegradation 3.2 Fullerene-Carbohydrate Hybrids for HIV-1 Protease Photodegradation 3.3 Fullerene-Sulfonic Acid Hybrid for Amyloid β Photodegradation 4 Carbohydrate-Photodegrading Organic Molecules 4.1 Small Organic Molecules for Oligosaccharide Photodegradation 4.2 Anthraquinone-Lectin Hybrids for Oligosaccharide Photodegradation 4.3 Anthraquinone-Boronic Acid Hybrids for Oligosaccharide Photodegradation 5 Conclusions

Original languageEnglish
Pages (from-to)2025-2052
Number of pages28
JournalSynlett
Volume23
Issue number14
DOIs
Publication statusPublished - 2012

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Photodegradation
Carbohydrates
Fullerenes
Molecules
DNA
Intercalating Agents
Anthraquinones
Proteins
Boronic Acids
Oligosaccharides
Enediynes
Steroid hormones
Lectins
Quinoxalines
Sulfonic Acids
Amyloid
Zinostatin
Degradation
Porphyrins
Guanine

Keywords

  • carbohydrate
  • DNA
  • photodegradation
  • protein
  • synthetic chemical biology

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

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title = "Design, synthesis and evaluation of light-activatable organic molecules that target-selectively degrade dna, proteins and carbohydrates; An interdisciplinary challenge for a synthetic organic chemist",
abstract = "We developed chemical methods for target-selective photodegradation of various biomacromolecules, including DNA, proteins, and carbohydrates. The DNA intercalator-carbohydrate moiety, without the enediyne structure found in the enediyne antibiotic neocarzinostatin chromophore, selectively degrades duplex DNA at guanine (G) nucleotides upon photoirradiation. Based on this finding, we designed and synthesized several artificial DNA intercalator-carbohydrate hybrids that can be photoactivated. Among them, several quinoxaline-carbohydrate hybrids were found to photodegrade duplex DNA at the G on the 5 side of 5-GG-3 sites. For protein degradation, we designed and synthesized several 2-phenylquinoline-steroid hormone hybrids and a porphyrin derivative, both of which selectively photodegrade the transcription factor estrogen receptor-α. In addition, we designed and synthesized fullerene-sugar and fullerene-sulfonic acid hybrids that selectively photodegrade HIV-1 protease and amyloid β, respectively. For carbohydrate degradation, we designed and synthesized anthraquinone-lectin hybrids and anthraquinone- and fullerene-boronic acid hybrids for selective photodegradation of target oligosaccharides having affinity for the lectin or boronic acid moiety of the hybrids. Furthermore, we successfully demonstrated practical uses for these light-activatable and molecular-targeted (LAMTA) molecules for controlling the function of DNA, proteins, and carbohydrates both in glass vessels and in cells. 1 Introduction 2 DNA Photodegrading Organic Molecules 2.1 DNA Intercalator-Carbohydrate Hybrids 2.2 Neocarzinostatin DNA Intercalator- Carbohydrate Hybrids for DNA Photodegradation 2.3 Quinoxaline-Carbohydrate Hybrids for DNA Photodegradation 3 Protein Photodegrading Organic Molecules 3.1 Quinoline-Steroid Hormone Hybrids for ER-α Photodegradation 3.2 Fullerene-Carbohydrate Hybrids for HIV-1 Protease Photodegradation 3.3 Fullerene-Sulfonic Acid Hybrid for Amyloid β Photodegradation 4 Carbohydrate-Photodegrading Organic Molecules 4.1 Small Organic Molecules for Oligosaccharide Photodegradation 4.2 Anthraquinone-Lectin Hybrids for Oligosaccharide Photodegradation 4.3 Anthraquinone-Boronic Acid Hybrids for Oligosaccharide Photodegradation 5 Conclusions",
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N2 - We developed chemical methods for target-selective photodegradation of various biomacromolecules, including DNA, proteins, and carbohydrates. The DNA intercalator-carbohydrate moiety, without the enediyne structure found in the enediyne antibiotic neocarzinostatin chromophore, selectively degrades duplex DNA at guanine (G) nucleotides upon photoirradiation. Based on this finding, we designed and synthesized several artificial DNA intercalator-carbohydrate hybrids that can be photoactivated. Among them, several quinoxaline-carbohydrate hybrids were found to photodegrade duplex DNA at the G on the 5 side of 5-GG-3 sites. For protein degradation, we designed and synthesized several 2-phenylquinoline-steroid hormone hybrids and a porphyrin derivative, both of which selectively photodegrade the transcription factor estrogen receptor-α. In addition, we designed and synthesized fullerene-sugar and fullerene-sulfonic acid hybrids that selectively photodegrade HIV-1 protease and amyloid β, respectively. For carbohydrate degradation, we designed and synthesized anthraquinone-lectin hybrids and anthraquinone- and fullerene-boronic acid hybrids for selective photodegradation of target oligosaccharides having affinity for the lectin or boronic acid moiety of the hybrids. Furthermore, we successfully demonstrated practical uses for these light-activatable and molecular-targeted (LAMTA) molecules for controlling the function of DNA, proteins, and carbohydrates both in glass vessels and in cells. 1 Introduction 2 DNA Photodegrading Organic Molecules 2.1 DNA Intercalator-Carbohydrate Hybrids 2.2 Neocarzinostatin DNA Intercalator- Carbohydrate Hybrids for DNA Photodegradation 2.3 Quinoxaline-Carbohydrate Hybrids for DNA Photodegradation 3 Protein Photodegrading Organic Molecules 3.1 Quinoline-Steroid Hormone Hybrids for ER-α Photodegradation 3.2 Fullerene-Carbohydrate Hybrids for HIV-1 Protease Photodegradation 3.3 Fullerene-Sulfonic Acid Hybrid for Amyloid β Photodegradation 4 Carbohydrate-Photodegrading Organic Molecules 4.1 Small Organic Molecules for Oligosaccharide Photodegradation 4.2 Anthraquinone-Lectin Hybrids for Oligosaccharide Photodegradation 4.3 Anthraquinone-Boronic Acid Hybrids for Oligosaccharide Photodegradation 5 Conclusions

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KW - carbohydrate

KW - DNA

KW - photodegradation

KW - protein

KW - synthetic chemical biology

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