Abstract
The utility of PEGylation for improving therapeutic protein pharmacology would be substantially expanded if the authentic protein drugs could be regenerated in vivo. Diminution of kinetic constants of both enzymes and protein ligands are commonly encountered following permanent bioconjugation with poly(ethylene glycol) polymers. In further development of releasable linker technology, we investigated an amino PEG anchimeric prodrug system, based on either the linear or branched bicin3 (BCN3) linkage, one promising representative of several aliphatic ester structures synthesized from N-modifed bis-2-hydroxyethylglycinamide (bicin). Protein models included an enzyme, lysozyme, and a receptor ligand, interferon-beta-1b, for preparation of linear or branched mono- and multi-PEGylated conjugates as inactive PEG-BCN3 prodrugs. The kinetics of protein release, both in plasma (in vitro) and in mice (in vivo), correlated with the number of PEG attachments, and the plasma half-lives of PEG release spanned a duration of hours to days within the therapeutically relevant window. Capillary electrophoresis, SDS-PAGE, mass determination, and enzymatic and antiviral activity determinations demonstrated regeneration of equivalent native proteins ...Continue Reading
References
Feb 1, 1981·Journal of Virology·S RubinsteinS Pestka
Jan 1, 1995·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·D Russell-HardeE Croze
Nov 13, 1998·Journal of Pharmaceutical Sciences·M J Roberts, J M Harris
Sep 10, 1999·Journal of Medicinal Chemistry·R B GreenwaldS Guan
Feb 12, 2000·Journal of Medicinal Chemistry·R B GreenwaldM Royzen
Aug 8, 2001·Journal of Controlled Release : Official Journal of the Controlled Release Society·R B Greenwald
Jan 19, 2002·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·M GraceR Bordens
Feb 5, 2003·Advanced Drug Delivery Reviews·Richard B GreenwaldCharles D Conover
Mar 4, 2003·Nature Reviews. Drug Discovery·J Milton Harris, Robert B Chess
Jun 25, 2003·Protein Expression and Purification·Stefan FoserThomas Schreitmüller
Jan 23, 2004·Journal of Medicinal Chemistry·Richard B GreenwaldAnthony Martinez
Jun 11, 2004·The Journal of Biological Chemistry·Haim TsuberyYoram Shechter
Sep 17, 2004·Journal of Medicinal Chemistry·Tal Peleg-ShulmanYoram Shechter
Apr 2, 2005·Nature Reviews. Drug Discovery·Sven Frokjaer, Daniel E Otzen
Citations
May 26, 2011·Pharmaceutical Research·Anna MeroGianfranco Pasut
Jun 18, 2009·Diabetes, Obesity & Metabolism·X MaX Luo
Apr 1, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Nadine HammerAchim M Goepferich
Jul 6, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Atul KolateAmbikanandan Misra
Apr 23, 2008·Expert Opinion on Drug Delivery·Sinéad M RyanDavid J Brayden
Nov 3, 2015·Journal of Pharmaceutical Sciences·Christian Reichert, Gerrit Borchard
Nov 19, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Gianfranco Pasut, Francesco M Veronese
Aug 4, 2015·ACS Applied Materials & Interfaces·Lei SongDejian Zhou
Sep 22, 2007·Advanced Drug Delivery Reviews·David Filpula, Hong Zhao
May 1, 2007·Biomolecular Engineering·David Filpula
Sep 23, 2010·Pharmaceutical Development and Technology·Robert W PayneMark Cornell Manning
Jan 24, 2015·Bioconjugate Chemistry·Yuhui GongMarc A Gauthier
May 31, 2011·Bioconjugate Chemistry·Jennifer ThomGraham Cotton
Jul 24, 2012·Molecular Pharmaceutics·Arghya PaulSatya Prakash
Nov 6, 2013·Bioconjugate Chemistry·Yutaka IkedaYukio Nagasaki
Aug 10, 2012·Bioconjugate Chemistry·Fei PengZhiguo Su
Dec 30, 2016·Molecular Pharmaceutics·Tatsunori HirotsuHidetoshi Arima
Jul 29, 2015·Biomaterials Science·Yuzhou WuTanja Weil
Oct 31, 2018·Organic & Biomolecular Chemistry·Sylvain UrsueguiAlain Wagner
Dec 7, 2007·Electrophoresis·Vladislav Dolník
Sep 9, 2011·Bioorganicheskaia khimiia·V P RomanovA I Miroshnikov
Sep 10, 2008·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Francesco M Veronese, Anna Mero
Aug 14, 2007·Soft Matter·Joris T MeijerJan C M van Hest
Dec 5, 2008·Bioconjugate Chemistry·Gianfranco PasutFrancesco M Veronese
Sep 10, 2009·Bioconjugate Chemistry·Chien-Hsing ChangDavid M Goldenberg
Dec 12, 2017·Bioconjugate Chemistry·Shoichiro AsayamaHiroyoshi Kawakami