Non-covalent albumin-binding ligands for extending the circulating half-life of small biotherapeutics

Published on Jun 6, 2019in MedChemComm2.807
· DOI :10.1039/C9MD00018F
Alessandro Zorzi5
Estimated H-index: 5
(EPFL: École Polytechnique Fédérale de Lausanne),
Sara Linciano2
Estimated H-index: 2
(Ca' Foscari University of Venice),
Alessandro Angelini18
Estimated H-index: 18
(Ca' Foscari University of Venice)
Sources
Abstract
Peptides and small protein scaffolds are gaining increasing interest as therapeutics. Similarly to full-length antibodies, they can bind a target with a high binding affinity and specificity while remaining small enough to diffuse into tissues. However, despite their numerous advantages, small biotherapeutics often suffer from a relatively short circulating half-life, thus requiring frequent applications that ultimately restrict their ease of use and user compliance. To overcome this limitation, a large variety of half-life extension strategies have been developed in the last decades. Linkage to ligands that non-covalently bind to albumin, the most abundant serum protein with a circulating half-life of ∼19 days in humans, represents one of the most successful approaches for the generation of long-lasting biotherapeutics with improved pharmacokinetic properties and superior efficacy in the clinic.
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