New proline, alanine, serine repeat sequence for pharmacokinetic enhancement of anti-VEGF single domain antibody

The Journal of Pharmacology and Experimental Therapeutics
Farnaz KhodabakhshReza Ahangari Cohan

Abstract

Therapeutic fragmented antibodies show a poor pharmacokinetic profile that leads to frequent high-dose administration. In the current study, for the first time, a novel proline, alanine, serine (PAS) repeat sequence, called PAS#208, was designed to extend the plasma half-life of a nano-sized anti-Vascular Endothelial Growth Factor-A single-domain antibody. Polyacrylamide gel electrophoresis, circular dichroism, dynamic light scattering, and electrophoretic light scattering were used to assess the physicochemical properties of the newly designed PAS sequence. The effect of PAS#208 on the biological activity of a single-domain antibody was studied using an in vitro proliferation assay. The pharmacokinetic parameters including terminal half-life, the volume of distribution, elimination rate constant, and clearance were determined in mice model and compared to the native protein and PAS#1(200) sequence. The novel PAS repeat sequence showed comparable physicochemical, biological, and pharmacokinetic features to the previously reported PAS#1(200) sequence. The PAS#208 increased the hydrodynamic radius and decreased significantly the electrophoretic mobility of the native protein without any change in zeta potential. Surprisingly, the...Continue Reading

References

Feb 24, 2006·Journal of Colloid and Interface Science·Jae Young KimByung Jun Yoon
Nov 17, 2009·Nature Biotechnology·Volker SchellenbergerWillem P C Stemmer
Jul 15, 2011·International Journal of Nanomedicine·Reza Ahangari CohanDariush Norouzian
Aug 25, 2011·Current Opinion in Biotechnology·Roland E Kontermann
Nov 10, 2011·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Ahmad MalekiHosnieh Tajerzadeh
Mar 19, 2013·Annual Review of Biochemistry·Serge Muyldermans
Jun 12, 2013·Protein Engineering, Design & Selection : PEDS·Martin SchlapschyArne Skerra
Dec 23, 2014·MAbs·Dawn M EckerHoward L Levine
Mar 27, 2015·Molecular Pharmaceutics·Volker MorathArne Skerra
Oct 27, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Vladimir N PodustVolker Schellenberger
Mar 1, 2008·Journal of Chemical Theory and Computation·Berk HessErik Lindahl
Jul 16, 2016·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Claudia Theresa MendlerMarkus Schwaiger
Jul 20, 2016·EBioMedicine·Isabel Van Audenhove, Jan Gettemans
Nov 12, 2016·Applied Microbiology and Biotechnology·Elizaveta A ZvonovaAlexander M Shuster
Nov 15, 2016·European Journal of Pharmacology·Zhexuan LinWenhong Luo
Aug 27, 2017·Artificial Cells, Nanomedicine, and Biotechnology·Farnaz KhodabakhshArdavan Mehdizadeh
Nov 23, 2017·Current Drug Delivery·Sajjad Ahmadpour, Seyed Jalal Hosseinimehr
Mar 10, 2018·Frontiers in Immunology·María Elena IezziGabriela Alicia Canziani
Mar 22, 2018·Oncology Research and Treatment·Katja Zirlik, Justus Duyster
Jan 9, 2019·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Jun 30, 2019·Journal of Controlled Release : Official Journal of the Controlled Release Society·Fabian BrandlAndreas Plückthun

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Citations

Jan 19, 2021·Preparative Biochemistry & Biotechnology·Farnaz KhodabakhshDariush Norouzian

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