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

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 peptide-based therapeutics.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Gebauer M,Skerra A

doi

10.1016/j.bmc.2017.09.016

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

2882-2887

issue

10

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(17)31328-7

journal_volume

26

pub_type

杂志文章

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