Affiliation:
1. School of Life Sciences and Medicine, Shandong University of Technology, Zibo, 255000, China
Abstract
Abstract:
Proteolysis-targeting chimeras (PROTACs) are an attractive means to target
previously undruggable or drug-resistant mutant proteins. While small molecule-based
PROTACs are stable and can cross cell membranes, there is limited availability of suitable
small molecule warheads capable of recruiting proteins to an E3 ubiquitin ligase for
degradation. With advances in structural biology and in silico protein structure prediction,
it is now becoming easier to define highly selective peptides suitable for PROTAC
design. As a result, peptide-based PROTACs are becoming a feasible proposition for targeting
previously “undruggable” proteins not amenable to small molecule inhibition. In
this review, we summarize recent progress in the design and application of peptide-based
PROTACs as well as several practical approaches for obtaining candidate peptides for
PROTACs. We also discuss the major hurdles preventing the translation of peptide-based
PROTACs from bench to bedside, such as their delivery and bioavailability, with the aim
of stimulating discussion about how best to accelerate the clinical development of peptide-
based PROTACs in the near future.
Funder
Natural Science Foundation of Shandong Province
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmacology,Molecular Medicine,Drug Discovery,Biochemistry,Organic Chemistry
Cited by
1 articles.
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