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  1. Article ; Online: Microwave-Induced Transient Heating Accelerates Protein PEGylation.

    Meziadi, Ahlem / Greschner, Andrea A / Gauthier, Marc A

    Biomacromolecules

    2023  Volume 24, Issue 6, Page(s) 2856–2863

    Abstract: PEGylation is one of the most widely employed strategies to increase the circulatory half-life of proteins and to reduce immune responses. However, conventional PEGylation protocols often require excess reagents and extended reaction times because of ... ...

    Abstract PEGylation is one of the most widely employed strategies to increase the circulatory half-life of proteins and to reduce immune responses. However, conventional PEGylation protocols often require excess reagents and extended reaction times because of their inefficiency. This study demonstrates that a microwave-induced transient heating phenomenon can be exploited to significantly accelerate protein PEGylation and even increase the degree of PEGylation achievable beyond what is possible at room temperature. This can be accomplished under conditions that do not compromise protein integrity. Several PEGylation chemistries and proteins are tested, and mechanistic insight is provided. Under certain conditions, extremely high levels of PEGylation were achieved in a matter of minutes. Moreover, considering the significantly reduced reaction times, the microwave-induced transient heating concept was adapted for continuous flow manufacturing of bioconjugates.
    MeSH term(s) Microwaves ; Heating/methods ; Proteins
    Chemical Substances Proteins
    Language English
    Publishing date 2023-05-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1526-4602
    ISSN (online) 1526-4602
    DOI 10.1021/acs.biomac.3c00250
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Overcoming PEG─Protein Mutual Repulsion to Improve the Efficiency of PEGylation.

    Meziadi, Ahlem / Zuberi, Navid / de Haan, Hendrick W / Gauthier, Marc A

    Biomacromolecules

    2022  Volume 23, Issue 11, Page(s) 4948–4956

    Abstract: Bioconjugation reactions, such as protein PEGylation, generally require excess reagents because of their inefficiency. Intriguingly, few reports have investigated the fundamental causes of this inefficiency. This study demonstrates that the excluded ... ...

    Abstract Bioconjugation reactions, such as protein PEGylation, generally require excess reagents because of their inefficiency. Intriguingly, few reports have investigated the fundamental causes of this inefficiency. This study demonstrates that the excluded volume effect (EVE)─caused by the mutual repulsion of methoxy poly(ethylene glycol) (mPEG) and proteins under typical PEGylation conditions─causes proteins and protein-reactive mPEG (5 kDa) to self-associate into separate "protein-rich" and "mPEG-rich" nano-domains (i.e., soluble self-assemblies). To overcome this obstacle to reaction, "unreactive" low-molecular-weight mPEG was added as a co-solvent to promote the association between the larger protein and the reactive mPEG molecules by harnessing the same EVE. The near complete PEGylation of lysozyme could be achieved with close to stoichiometric amounts of reactive mPEG, and beneficial effects were observed for other proteins. Considering the general nature of the EVE (e.g., salting-out and PEGying-out), this study provides important perspectives on enhancing bioconjugation reactions, which are relevant to many nanoscale systems.
    MeSH term(s) Polyethylene Glycols/metabolism ; Proteins ; Molecular Weight
    Chemical Substances monomethoxypolyethylene glycol (9004-74-4) ; Polyethylene Glycols (3WJQ0SDW1A) ; Proteins
    Language English
    Publishing date 2022-10-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1526-4602
    ISSN (online) 1526-4602
    DOI 10.1021/acs.biomac.2c01192
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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