Enhancing bioactivity, physicochemical, and pharmacokinetic properties of a nano-sized, anti-VEGFR2 Adnectin, through PASylation technology

Scientific Reports
Safieh AghaabdollahianSakineh Latif Dizaji

Abstract

The crucial role of VEGF receptor 2 (VEGFR2) signaling in the angiogenesis and metastasis of solid tumors has prompted the development of inhibitors with minimal bystander effects. Recently, Adnectin C has attracted attention for cancer treatment. To overcome the problematic properties of Adnectin, a novel form of Adnectin C has been designed by its fusion to a biodegradable polymeric peptide containing Pro/Ala/Ser (PAS) repetitive residues. E. coli-expressed recombinant fused and unfused proteins were compared in terms of bioactivity, physicochemical, and pharmacokinetic properties using standard methods. Dynamic light scattering (DLS) analysis of PASylated adnectin C revealed an approximate 2-fold increase in particle size with a slight change in the net charge. Additionally, fusion of the PAS sequence improved its stability against the growth of thermo-induced aggregated forms. The high receptor-binding and improved binding kinetic parameters of PASylated Adnectin C was confirmed by ELISA and surface plasmon resonance assays, respectively. Pharmacokinetic studies showed a noticeable increase in the terminal half-life of Adnectin C-PAS#1(200) by a factor of 4.57 after single dose by intravenous injection into female BALB/c mi...Continue Reading

References

Mar 21, 2006·Vascular Pharmacology·Nilesh M PandyaDev D Santani
Apr 7, 2006·Protein Science : a Publication of the Protein Society·Rahul S RajanDavid N Brems
Jun 8, 2007·Blood Cells, Molecules & Diseases·Zaher K OtrockAli I Shamseddine
Jun 27, 2009·Accounts of Chemical Research·Megan E FoxJean M J Fréchet
Nov 17, 2009·Nature Biotechnology·Volker SchellenbergerWillem P C Stemmer
Dec 31, 2009·Journal of Dental Research·V UskokovicS Habelitz
Jan 6, 2010·Journal of Pharmaceutical Sciences·Dipak S PisalSathy V Balu-Iyer
Feb 5, 2010·Biotechnology Letters·A ConstantinouM P Deonarain
Nov 12, 2010·Protein Engineering, Design & Selection : PEDS·D Lipovsek
Jan 13, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anthony W TolcherMonica Mita
Jul 6, 2011·Current Opinion in Biotechnology·John LöfblomStefan Ståhl
Feb 14, 2012·Structure·Vidhyashankar RamamurthySteven Sheriff
Jun 9, 2012·Journal of Pharmaceutical Sciences·Jeffrey L ClelandVolker Schellenberger
Jun 12, 2012·Bioconjugate Chemistry·Chen ChenMahendra P Deonarain
Aug 9, 2012·Langmuir : the ACS Journal of Surfaces and Colloids·Dianlu JiangFeimeng Zhou
Aug 25, 2012·Future Medicinal Chemistry·Verena M AhrensAnnette G Beck-Sickinger
Jun 12, 2013·Protein Engineering, Design & Selection : PEDS·Martin SchlapschyArne Skerra
Aug 3, 2013·The Journal of Clinical Investigation·Jonathan WeltiPeter Carmeliet
Aug 21, 2013·PloS One·Yascara Grisel Luna SaavedraNabil G Seidah
Sep 11, 2013·Proceedings of the National Academy of Sciences of the United States of America·Arianna RathCharles M Deber
Oct 18, 2013·Protein Engineering, Design & Selection : PEDS·Vladimir N PodustVolker Schellenberger
Oct 26, 2013·Critical Reviews in Biotechnology·Timo RathRichard S Blumberg
Dec 18, 2013·Biological & Pharmaceutical Bulletin·Fan ZhangHai-tong Wan
Mar 29, 2014·Biologics : Targets & Therapy·Nataša Skalko-Basnet
Jun 12, 2014·The Journal of Pharmacology and Experimental Therapeutics·Tracy MitchellRex A Parker
Jun 17, 2014·Bioconjugate Chemistry·Sheng DingVolker Schellenberger
Jun 26, 2014·Journal of Visualized Experiments : JoVE·Calvin R JustusLi V Yang
Sep 10, 2014·Critical Reviews in Oncology/hematology·Roeland LamerisHans J van der Vliet
Feb 5, 2015·International Journal of Environmental Research and Public Health·Sondra S Teske, Corrella S Detweiler
May 23, 2015·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Claudia T MendlerArne Skerra
Jul 17, 2015·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·William R Strohl
Oct 27, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Vladimir N PodustVolker Schellenberger
Nov 12, 2016·Applied Microbiology and Biotechnology·Elizaveta A ZvonovaAlexander M Shuster
Aug 27, 2017·Artificial Cells, Nanomedicine, and Biotechnology·Farnaz KhodabakhshArdavan Mehdizadeh
Jun 1, 2018·Protein and Peptide Letters·Huizi Wu, Jiaguo Huang
Sep 25, 2018·Protein Engineering, Design & Selection : PEDS·Daša LipovšekJames W Bryson

❮ Previous
Next ❯

Citations

Apr 24, 2019·The Journal of Pharmacology and Experimental Therapeutics·A R Satvik IyengarAbhay H Pande
Jan 10, 2020·Annual Review of Pharmacology and Toxicology·Michaela Gebauer, Arne Skerra
Oct 25, 2020·Pharmaceutics·Nkiruka IbeanuSahar Awwad
Oct 30, 2020·Scientific Reports·Somayeh MazaheriFatemeh Torkashvand
Feb 6, 2020·Trends in Biochemical Sciences·Zachary R CrookJames M Olson
Feb 23, 2021·The Journal of Biological Chemistry·Peter G ChandlerAshley M Buckle

❮ Previous
Next ❯

Methods Mentioned

BETA
electrophoresis
Differential Scanning Calorimetry
ELISA
chip
restriction
reverse phase chromatography
surface
biosensor

Software Mentioned

Prism
Biacore X100
ImageJ
Data Explorer

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.