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Glycoengineering of Therapeutic Antibodies with Small Molecule Inhibitors.
Li, Shasha; McCraw, Alex J; Gardner, Richard A; Spencer, Daniel I R; Karagiannis, Sophia N; Wagner, Gerd K.
  • Li S; Medical Biology Centre, School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.
  • McCraw AJ; St. John's Institute of Dermatology, School of Basic & Medical Biosciences, King's College London, 9th Floor Tower Wing, Guy's Hospital, London SE1 9RT, UK.
  • Gardner RA; St. John's Institute of Dermatology, School of Basic & Medical Biosciences, King's College London, 9th Floor Tower Wing, Guy's Hospital, London SE1 9RT, UK.
  • Spencer DIR; Ludger, Ltd., Culham Science Centre, Abingdon, Oxfordshire OX14 3EB, UK.
  • Karagiannis SN; Ludger, Ltd., Culham Science Centre, Abingdon, Oxfordshire OX14 3EB, UK.
  • Wagner GK; St. John's Institute of Dermatology, School of Basic & Medical Biosciences, King's College London, 9th Floor Tower Wing, Guy's Hospital, London SE1 9RT, UK.
Antibodies (Basel) ; 10(4)2021 Nov 04.
Article in English | MEDLINE | ID: covidwho-1595331
ABSTRACT
Monoclonal antibodies (mAbs) are one of the cornerstones of modern medicine, across an increasing range of therapeutic areas. All therapeutic mAbs are glycoproteins, i.e., their polypeptide chain is decorated with glycans, oligosaccharides of extraordinary structural diversity. The presence, absence, and composition of these glycans can have a profound effect on the pharmacodynamic and pharmacokinetic profile of individual mAbs. Approaches for the glycoengineering of therapeutic mAbs-the manipulation and optimisation of mAb glycan structures-are therefore of great interest from a technological, therapeutic, and regulatory perspective. In this review, we provide a brief introduction to the effects of glycosylation on the biological and pharmacological functions of the five classes of immunoglobulins (IgG, IgE, IgA, IgM and IgD) that form the backbone of all current clinical and experimental mAbs, including an overview of common mAb expression systems. We review selected examples for the use of small molecule inhibitors of glycan biosynthesis for mAb glycoengineering, we discuss the potential advantages and challenges of this approach, and we outline potential future applications. The main aim of the review is to showcase the expanding chemical toolbox that is becoming available for mAb glycoengineering to the biology and biotechnology community.
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Full text: Available Collection: International databases Database: MEDLINE Language: English Year: 2021 Document Type: Article Affiliation country: Antib10040044

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Full text: Available Collection: International databases Database: MEDLINE Language: English Year: 2021 Document Type: Article Affiliation country: Antib10040044