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  1. Article ; Online: Editorial for the Special Issue 'Synthetic Biology and Biomimicry'.

    Zelikin, Alexander N / Andersen, Ebbe Sloth / Städler, Brigitte

    Small (Weinheim an der Bergstrasse, Germany)

    2023  Volume 19, Issue 13, Page(s) e2301160

    MeSH term(s) Synthetic Biology ; Biomimetics
    Language English
    Publishing date 2023-03-08
    Publishing country Germany
    Document type Editorial
    ZDB-ID 2168935-0
    ISSN 1613-6829 ; 1613-6810
    ISSN (online) 1613-6829
    ISSN 1613-6810
    DOI 10.1002/smll.202301160
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  2. Article ; Online: Unique enzymatic repertoire reveals the tumour.

    Zelikin, Alexander N

    Nature chemistry

    2019  Volume 12, Issue 1, Page(s) 11–12

    MeSH term(s) Gold ; Humans ; Nanostructures ; Neoplasms ; Sequence Analysis, DNA
    Chemical Substances Gold (7440-57-5)
    Language English
    Publishing date 2019-12-10
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 2464596-5
    ISSN 1755-4349 ; 1755-4330
    ISSN (online) 1755-4349
    ISSN 1755-4330
    DOI 10.1038/s41557-019-0400-0
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  3. Article ; Online: Mechanisms of Degradation for Polydisulfides: Main Chain Scission, Self-Immolation, Or Chain Transfer Depolymerization.

    Kristensen, Maria Merrild / Løvschall, Kaja Borup / Zelikin, Alexander N

    ACS macro letters

    2023  Volume 12, Issue 7, Page(s) 955–960

    Abstract: Organic polydisulfides hold immense potential for the design of recyclable materials. Of these, polymers based on lipoic acid are attractive, as they are based on a natural, renewable resource. Herein, we demonstrate that reductive degradation of lipoic ... ...

    Abstract Organic polydisulfides hold immense potential for the design of recyclable materials. Of these, polymers based on lipoic acid are attractive, as they are based on a natural, renewable resource. Herein, we demonstrate that reductive degradation of lipoic acid polydisulfides is a rapid process whereby the quantity of added initiator relative to the polymer content defines the mechanism of polymer degradation, through the main chain scission, self-immolation, or "chain transfer" depolymerization. The latter mechanism is defined as the one during which a thiol group released through the decomposition of one polydisulfide chain initiates depolymerization of the neighbor macromolecule. The chain transfer mechanism afforded the highest yields of recovery of the monomer in its pristine form, and just one molecule of the reducing agent to initiate polymer degradation afforded recovery of over 50% of the monomer. These data are important to facilitate the development of polymer recycling and monomer reuse schemes.
    Language English
    Publishing date 2023-06-29
    Publishing country United States
    Document type Journal Article
    ISSN 2161-1653
    ISSN (online) 2161-1653
    DOI 10.1021/acsmacrolett.3c00345
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  4. Article ; Online: Chemical Zymogens: Specificity and Steroidal Control of Reactivation.

    Casanovas Montasell, Mireia / Baumann, Anna / Zelikin, Alexander N

    Chembiochem : a European journal of chemical biology

    2023  Volume 24, Issue 15, Page(s) e202300304

    Abstract: Activating and masking enzymatic activity on demand is of the highest importance in nature. It is achieved by chemical interconversion of enzymes and the corresponding zymogens through, for example, proteolytic processing or reversible phosphorylation, ... ...

    Abstract Activating and masking enzymatic activity on demand is of the highest importance in nature. It is achieved by chemical interconversion of enzymes and the corresponding zymogens through, for example, proteolytic processing or reversible phosphorylation, and affords on-demand activation of enzymes, controlled in space and/or time. In stark contrast, examples of chemical zymogens are very few, and in most cases these are based on disulfide chemistry, which is largely indiscriminate as to the nature of the activating thiol. In this work, we address an outstanding challenge of specificity of reactivation of chemical zymogens. We achieve this through engineering affinity between the chemical zymogen and the activator. Additional, higher-level control over zymogen reactivation is installed in a nature-mimicking approach using steroidal hormones. Taken together, the results of this study take a step towards establishing the specificity of reactivation of synthetic, chemical zymogens. We anticipate that the results of this study will contribute significantly to the development of chemical zymogens as tools for diverse use in chemical biology and biotechnology.
    MeSH term(s) Enzyme Precursors
    Chemical Substances Enzyme Precursors
    Language English
    Publishing date 2023-06-28
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2020469-3
    ISSN 1439-7633 ; 1439-4227
    ISSN (online) 1439-7633
    ISSN 1439-4227
    DOI 10.1002/cbic.202300304
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  5. Article ; Online: Chemical (neo)glycosylation of biological drugs.

    Walther, Raoul / Zelikin, Alexander N

    Advanced drug delivery reviews

    2021  Volume 171, Page(s) 62–76

    Abstract: Biological drugs, specifically proteins and peptides, are a privileged class of medicinal agents and are characterized with high specificity and high potency of therapeutic activity. However, biologics are fragile and require special care during storage, ...

    Abstract Biological drugs, specifically proteins and peptides, are a privileged class of medicinal agents and are characterized with high specificity and high potency of therapeutic activity. However, biologics are fragile and require special care during storage, and are often modified to optimize their pharmacokinetics in terms of proteolytic stability and blood residence half-life. In this review, we showcase glycosylation as a method to optimize biologics for storage and application. Specifically, we focus on chemical glycosylation as an approach to modify biological drugs. We present case studies that illustrate the success of this methodology and specifically address the highly important question: does connectivity within the glycoconjugate have to be native or not? We then present the innovative methods of chemical glycosylation of biologics and specifically highlight the emerging and established protecting group-free methodologies of glycosylation. We discuss thermodynamic origins of protein stabilization via glycosylation, and analyze in detail stabilization in terms of proteolytic stability, aggregation upon storage and/or heat treatment. Finally, we present a case study of protein modification using sialic acid-containing glycans to avoid hepatic clearance of biological drugs. This review aims to spur interest in chemical glycosylation as a facile, powerful tool to optimize proteins and peptides as medicinal agents.
    MeSH term(s) Animals ; Biological Products/chemistry ; Biological Products/pharmacology ; Erythropoietin/chemistry ; Erythropoietin/pharmacology ; Glycosylation ; Humans ; Islet Amyloid Polypeptide/chemistry ; Islet Amyloid Polypeptide/pharmacology ; N-Acetylneuraminic Acid/chemistry ; N-Acetylneuraminic Acid/pharmacology ; Polysaccharides/chemistry ; Polysaccharides/pharmacology
    Chemical Substances Biological Products ; Islet Amyloid Polypeptide ; Polysaccharides ; Erythropoietin (11096-26-7) ; pramlintide (D3FM8FA78T) ; N-Acetylneuraminic Acid (GZP2782OP0)
    Language English
    Publishing date 2021-02-03
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 639113-8
    ISSN 1872-8294 ; 0169-409X
    ISSN (online) 1872-8294
    ISSN 0169-409X
    DOI 10.1016/j.addr.2021.01.021
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2241: Show issues Location:
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    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: Broad-Spectrum Antiviral Agents Based on Multivalent Inhibitors of Viral Infectivity.

    Zelikin, Alexander N / Stellacci, Francesco

    Advanced healthcare materials

    2021  Volume 10, Issue 6, Page(s) e2001433

    Abstract: The ongoing pandemic of the coronavirus disease (Covid-19), caused by the spread of the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), highlights the need for broad-spectrum antiviral drugs. In this Essay, it is argued that such agents ... ...

    Abstract The ongoing pandemic of the coronavirus disease (Covid-19), caused by the spread of the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), highlights the need for broad-spectrum antiviral drugs. In this Essay, it is argued that such agents already exist and are readily available while highlighting the challenges that remain to translate them into the clinic. Multivalent inhibitors of viral infectivity based on polymers or supramolecular agents and nanoparticles are shown to be broadly acting against diverse pathogens in vitro as well as in vivo. Furthermore, uniquely, such agents can be virucidal. Polymers and nanoparticles are stable, do not require cold chain of transportation and storage, and can be obtained on large scale. Specifically, for the treatment of respiratory viruses and pulmonary diseases, these agents can be administered via inhalation/nebulization, as is currently investigated in clinical trials as a treatment against SARS CoV-2/Covid-19. It is believed that with due optimization and clinical validation, multivalent inhibitors of viral infectivity can claim their rightful position as broad-spectrum antiviral agents.
    MeSH term(s) Antibodies, Neutralizing/therapeutic use ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; COVID-19/pathology ; COVID-19/virology ; Humans ; Nanoparticles/chemistry ; Nanoparticles/toxicity ; Polymers/chemistry ; Polymers/pharmacology ; SARS-CoV-2/drug effects ; SARS-CoV-2/isolation & purification ; Virus Diseases/drug therapy ; Virus Internalization/drug effects ; COVID-19 Drug Treatment
    Chemical Substances Antibodies, Neutralizing ; Antiviral Agents ; Polymers
    Language English
    Publishing date 2021-01-25
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2649576-4
    ISSN 2192-2659 ; 2192-2640
    ISSN (online) 2192-2659
    ISSN 2192-2640
    DOI 10.1002/adhm.202001433
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6966: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  7. Article ; Online: Artificial Biology: Molecular Design and Cell Mimicry.

    Zelikin, Alexander N / Städler, Brigitte

    Small (Weinheim an der Bergstrasse, Germany)

    2020  Volume 16, Issue 27, Page(s) e2003442

    MeSH term(s) Artificial Cells/metabolism ; Biology/trends ; Biomimetics/standards ; Biomimetics/trends ; Molecular Mimicry
    Keywords covid19
    Language English
    Publishing date 2020-07-08
    Publishing country Germany
    Document type Editorial ; Introductory Journal Article
    ZDB-ID 2168935-0
    ISSN 1613-6829 ; 1613-6810
    ISSN (online) 1613-6829
    ISSN 1613-6810
    DOI 10.1002/smll.202003442
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  8. Article ; Online: Nitric Oxide to Fight Viral Infections.

    Lisi, Fabio / Zelikin, Alexander N / Chandrawati, Rona

    Advanced science (Weinheim, Baden-Wurttemberg, Germany)

    2021  Volume 8, Issue 7, Page(s) 2003895

    Abstract: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that has quickly and deeply affected the world, with over 60 million confirmed cases. There has been a great effort ... ...

    Abstract Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that has quickly and deeply affected the world, with over 60 million confirmed cases. There has been a great effort worldwide to contain the virus and to search for an effective treatment for patients who become critically ill with COVID-19. A promising therapeutic compound currently undergoing clinical trials for COVID-19 is nitric oxide (NO), which is a free radical that has been previously reported to inhibit the replication of several DNA and RNA viruses, including coronaviruses. Although NO has potent antiviral activity, it has a complex role in the immunological host responses to viral infections, i.e., it can be essential for pathogen control or detrimental for the host, depending on its concentration and the type of virus. In this Essay, the antiviral role of NO against SARS-CoV, SARS-CoV-2, and other human viruses is highlighted, current development of NO-based therapies used in the clinic is summarized, existing challenges are discussed and possible further developments of NO to fight viral infections are suggested.
    MeSH term(s) Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; COVID-19/diagnosis ; COVID-19/virology ; Clinical Trials as Topic ; Humans ; Nitric Oxide/pharmacology ; Nitric Oxide/therapeutic use ; Nitric Oxide Synthase Type II/antagonists & inhibitors ; Nitric Oxide Synthase Type II/metabolism ; SARS-CoV-2/drug effects ; SARS-CoV-2/isolation & purification ; Virus Diseases/drug therapy ; Virus Diseases/pathology ; Virus Replication/drug effects ; COVID-19 Drug Treatment
    Chemical Substances Antiviral Agents ; Nitric Oxide (31C4KY9ESH) ; Nitric Oxide Synthase Type II (EC 1.14.13.39)
    Language English
    Publishing date 2021-02-09
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2808093-2
    ISSN 2198-3844 ; 2198-3844
    ISSN (online) 2198-3844
    ISSN 2198-3844
    DOI 10.1002/advs.202003895
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  10. Article ; Online: Enzyme Mimics for the Catalytic Generation of Nitric Oxide from Endogenous Prodrugs.

    Yang, Tao / Zelikin, Alexander N / Chandrawati, Rona

    Small (Weinheim an der Bergstrasse, Germany)

    2020  Volume 16, Issue 27, Page(s) e1907635

    Abstract: The highly diverse biological roles of nitric oxide (NO) in both physiological and pathophysiological processes have prompted great interest in the use of NO as a therapeutic agent in various biomedical applications. NO can exert either protective or ... ...

    Abstract The highly diverse biological roles of nitric oxide (NO) in both physiological and pathophysiological processes have prompted great interest in the use of NO as a therapeutic agent in various biomedical applications. NO can exert either protective or deleterious effects depending on its concentration and the location where it is delivered or generated. This double-edged attribute, together with the short half-life of NO in biological systems, poses a major challenge to the realization of the full therapeutic potential of this molecule. Controlled release strategies show an admirable degree of precision with regard to the spatiotemporal dosing of NO but are disadvantaged by the finite NO deliverable payload. In turn, enzyme-prodrug therapy techniques afford enhanced deliverable payload but are troubled by the inherent low stability of natural enzymes, as well as the requirement to control pharmacokinetics for the exogenous prodrugs. The past decade has seen the advent of a new paradigm in controlled delivery of NO, namely localized bioconversion of the endogenous prodrugs of NO, specifically by enzyme mimics. These early developments are presented, successes of this strategy are highlighted, and possible future work on this avenue of research is critically discussed.
    MeSH term(s) Biomimetic Materials/chemistry ; Catalysis ; Drug Delivery Systems ; Enzymes/chemistry ; Humans ; Nitric Oxide/chemistry ; Nitric Oxide/metabolism ; Prodrugs/chemistry
    Chemical Substances Enzymes ; Prodrugs ; Nitric Oxide (31C4KY9ESH)
    Language English
    Publishing date 2020-05-05
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2168935-0
    ISSN 1613-6829 ; 1613-6810
    ISSN (online) 1613-6829
    ISSN 1613-6810
    DOI 10.1002/smll.201907635
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