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Supramolecular PEGylation of biopharmaceuticals

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Show simple item record Vinciguerra, Brittany Thapa, Lavanya S. Jhunjhunwala, Siddharth Isaacs, Lyle Webber, Matthew Appel, Eric Cortinas, Abel Bryan Langer, Robert S Anderson, Daniel Griffith 2017-09-13T20:03:38Z 2017-09-13T20:03:38Z 2016-11 2016-07
dc.identifier.issn 0027-8424
dc.identifier.issn 1091-6490
dc.description.abstract The covalent modification of therapeutic biomolecules has been broadly explored, leading to a number of clinically approved modified protein drugs. These modifications are typically intended to address challenges arising in biopharmaceutical practice by promoting improved stability and shelf life of therapeutic proteins in formulation, or modifying pharmacokinetics in the body. Toward these objectives, covalent modification with poly(ethylene glycol) (PEG) has been a common direction. Here, a platform approach to biopharmaceutical modification is described that relies on noncovalent, supramolecular host–guest interactions to endow proteins with prosthetic functionality. Specifically, a series of cucurbit[7]uril (CB[7])–PEG conjugates are shown to substantially increase the stability of three distinct protein drugs in formulation. Leveraging the known and high-affinity interaction between CB[7] and an N-terminal aromatic residue on one specific protein drug, insulin, further results in altering of its pharmacological properties in vivo by extending activity in a manner dependent on molecular weight of the attached PEG chain. Supramolecular modification of therapeutic proteins affords a noncovalent route to modify its properties, improving protein stability and activity as a formulation excipient. Furthermore, this offers a modular approach to append functionality to biopharmaceuticals by noncovalent modification with other molecules or polymers, for applications in formulation or therapy. en_US
dc.description.sponsorship Leona M. and Harry B. Helmsley Charitable Trust (Award 2014PG-T1D002) en_US
dc.language.iso en_US
dc.publisher National Academy of Sciences (U.S.) en_US
dc.relation.isversionof en_US
dc.rights Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. en_US
dc.source PNAS en_US
dc.title Supramolecular PEGylation of biopharmaceuticals en_US
dc.type Article en_US
dc.identifier.citation Webber, Matthew J. et al. “Supramolecular PEGylation of Biopharmaceuticals.” Proceedings of the National Academy of Sciences 113, 50 (December 2016): 14189–14194 © 2016 National Academy of Sciences en_US
dc.contributor.department David H. Koch Institute for Integrative Cancer Research at MIT en_US
dc.contributor.department Massachusetts Institute of Technology. Department of Chemical Engineering en_US
dc.contributor.department Harvard University--MIT Division of Health Sciences and Technology en_US
dc.contributor.department Institute for Medical Engineering and Science en_US
dc.contributor.mitauthor Webber, Matthew
dc.contributor.mitauthor Appel, Eric
dc.contributor.mitauthor Cortinas, Abel Bryan
dc.contributor.mitauthor Langer, Robert S
dc.contributor.mitauthor Anderson, Daniel Griffith
dc.relation.journal Proceedings of the National Academy of Sciences en_US
dc.identifier.mitlicense PUBLISHER_POLICY en_US
dc.eprint.version Final published version en_US
dc.type.uri en_US
eprint.status en_US
dspace.orderedauthors Webber, Matthew J.; Appel, Eric A.; Vinciguerra, Brittany; Cortinas, Abel B.; Thapa, Lavanya S.; Jhunjhunwala, Siddharth; Isaacs, Lyle; Langer, Robert; Anderson, Daniel G. en_US
dspace.embargo.terms N en_US

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