Prospects of PASylation® for the design of protein and peptide therapeutics with extended half-life and enhanced action

Bioorganic & Medicinal Chemistry
Michaela Gebauer, Arne Skerra

Abstract

Pharmacokinetic (PK) extension is no longer just a means to create improved second generation biologics (so-called biobetters), but constitutes an accepted strategy in biopharmaceutical drug development today. Although PEGylation has become a widely applied methodology to furnish therapeutic proteins and peptides with prolonged plasma half-life, the immunogenicity and missing biodegradability of this synthetic polymer has prompted an evident need for alternatives. PASylation is based on biological polypeptides made of the small l-amino acids Pro, Ala and/or Ser (PAS), which adopt a random coil structure in aqueous buffers with surprisingly similar biophysical properties as PEG. In contrast, PAS sequences can be conjugated to pharmaceutically active proteins and peptides both via chemical coupling and at the genetic level, as so-called fusion proteins. PASylation has been successfully applied to numerous biologics, including cytokines, growth factors, antibody fragments, enzymes as well as various peptides, and validated in diverse animal models, from mice to monkeys. Here we compare PASylation with other current strategies for half-life extension and we discuss the utility of these approaches for the design of innovative peptid...Continue Reading

Citations

Feb 8, 2019·Current Pharmaceutical Design·Huanbo TanPeijian Zou
Apr 24, 2019·The Journal of Pharmacology and Experimental Therapeutics·A R Satvik IyengarAbhay H Pande
Jul 7, 2020·Acta Crystallographica. Section F, Structural Biology Communications·André SchiefnerArne Skerra
Jul 17, 2020·The Journal of Pharmacology and Experimental Therapeutics·Farnaz KhodabakhshReza Ahangari Cohan
Mar 3, 2020·Frontiers in Bioengineering and Biotechnology·Filippo MoncalvoFrancesco Cellesi
Jan 29, 2019·Frontiers in Bioengineering and Biotechnology·Larissa Pereira BrumanoAdalberto Pessoa Junior
Dec 14, 2018·Nature Reviews. Drug Discovery·Iriny EkladiousMark W Grinstaff
Jan 19, 2021·Preparative Biochemistry & Biotechnology·Farnaz KhodabakhshDariush Norouzian
Dec 18, 2020·Frontiers in Molecular Biosciences·Alex Bunker, Tomasz Róg
Dec 31, 2020·International Journal of Molecular Sciences·Uli Binder, Arne Skerra
Apr 2, 2021·Biomacromolecules·Michael TullyRainer Haag
Jul 27, 2021·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Ange B IlangalaGéraldine Piel
Aug 31, 2021·Drug Discovery Today·Karin M Torres-ObrequeCarlota O Rangel-Yagui
Dec 29, 2021·Archives of Toxicology·Lisa StiglerTimo Wille
Jan 16, 2022·Communications Biology·Kenichiro ItoAtsushi Konishi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cajal Bodies & Gems

Cajal bodies or coiled bodies are dense foci of coilin protein. Gemini of Cajal bodies, or gems, are microscopically similar to Cajal bodies. It is believed that Cajal bodies play important roles in RNA processing while gems assist the Cajal bodies. Find the latest research on Cajal bodies and gems here.