Engineered protein scaffolds as leads for synthetic inhibitors of protein–protein interactions

Michael G. Wuo, Paramjit Arora

Research output: Contribution to journalReview article

Abstract

Rationally designed protein–protein interaction inhibitors mimic interfacial binding epitopes, specifically residues that contribute significantly to binding. However, direct mimicry often does not lead to high affinity ligands because the natural complexes themselves are functionally transient and of low affinity. The mimics typically need to be optimized for potency. Engineered proteins displaying conformationally-defined epitopes may serve as attractive alternatives to natural protein partners as they can be strictly screened for tight binding. The advantage of focused screens with conformationally-defined protein scaffolds is that conservation of the geometry of the natural binding epitopes may preserve binding site specificity while allowing direct mimicry by various synthetic secondary structure scaffolds. Here we review different classes of engineered proteins for their binding epitope geometry and as leads for synthetic secondary and tertiary structure mimics.

Original languageEnglish (US)
Pages (from-to)16-22
Number of pages7
JournalCurrent Opinion in Chemical Biology
Volume44
DOIs
StatePublished - Jun 1 2018

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Scaffolds
Epitopes
Proteins
Geometry
Protein Binding
Conservation
Binding Sites
Ligands

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry

Cite this

Engineered protein scaffolds as leads for synthetic inhibitors of protein–protein interactions. / Wuo, Michael G.; Arora, Paramjit.

In: Current Opinion in Chemical Biology, Vol. 44, 01.06.2018, p. 16-22.

Research output: Contribution to journalReview article

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