PASylation: a biological alternative to PEGylation for extending the plasma half-life of pharmaceutically active proteins
Martin Schlapschy,Uli Binder,Claudia Börger,Ina Theobald,Klaus Wachinger,Sigrid Kisling,Dirk Haller,Arne Skerra +7 more
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It is demonstrated that PASylation bestows typical biologics, such as interferon, growth hormone or Fab fragments, with considerably prolonged circulation and boosts bioactivity in vivo.Abstract:
A major limitation of biopharmaceutical proteins is their fast clearance from circulation via kidney filtration, which strongly hampers efficacy both in animal studies and in human therapy. We have developed conformationally disordered polypeptide chains with expanded hydrodynamic volume comprising the small residues Pro, Ala and Ser (PAS). PAS sequences are hydrophilic, uncharged biological polymers with biophysical properties very similar to poly-ethylene glycol (PEG), whose chemical conjugation to drugs is an established method for plasma half-life extension. In contrast, PAS polypeptides offer fusion to a therapeutic protein on the genetic level, permitting Escherichia coli production of fully active proteins and obviating in vitro coupling or modification steps. Furthermore, they are biodegradable, thus avoiding organ accumulation, while showing stability in serum and lacking toxicity or immunogenicity in mice. We demonstrate that PASylation bestows typical biologics, such as interferon, growth hormone or Fab fragments, with considerably prolonged circulation and boosts bioactivity in vivo.read more
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Nanoparticle Probes for the Detection of Cancer Biomarkers, Cells, and Tissues by Fluorescence
Alyssa B. Chinen,Chenxia M. Guan,Jennifer R. Ferrer,Stacey N. Barnaby,Timothy J. Merkel,Chad A. Mirkin +5 more
TL;DR: Overcoming Limitations in Nanoparticle Drug Delivery: Triggered, Intravascular Release to Improve Drug Penetration into Tumors and Design Considerations for Tumour-Targeted Nanoparticles.
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The Current State of Peptide Drug Discovery: Back to the Future?
TL;DR: An emphasis is placed on describing research efforts to overcome the inherent weaknesses of peptide drugs, in particular their poor pharmacokinetic properties, and how these efforts have been critical to the discovery, design, and subsequent development of novel therapeutics.
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Proteins. Structures and molecular properties, T.E. Creighton. W. H. Freeman and Company, New York (1984), 515, $36.95
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Anti-PEG antibodies in the clinic: Current issues and beyond PEGylation.
TL;DR: A number of clinical reports and some critical animal studies regarding pre-existing and treatment-induced anti-PEG Abs and several protein modification technologies beyond PEGylation were provided.
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Fusion Proteins for Half-Life Extension of Biologics as a Strategy to Make Biobetters
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