Next Article in Journal
FAM83G Is a Novel Inducer of Apoptosis
Previous Article in Journal
Effects of Rich in Β-Glucans Edible Mushrooms on Aging Gut Microbiota Characteristics: An In Vitro Study
Previous Article in Special Issue
Anti-Biofilm Effects of Synthetic Antimicrobial Peptides Against Drug-Resistant Pseudomonas aeruginosa and Staphylococcus aureus Planktonic Cells and Biofilm
 
 
Review

Application of Post Solid-Phase Oxime Ligation to Fine-Tune Peptide–Protein Interactions

1
Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA
2
Discovery Chemistry, Novo Nordisk Research Center Seattle, Seattle, WA 98109, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Jacques Lebreton
Molecules 2020, 25(12), 2807; https://doi.org/10.3390/molecules25122807
Received: 18 May 2020 / Revised: 10 June 2020 / Accepted: 14 June 2020 / Published: 18 June 2020
(This article belongs to the Special Issue Peptide-Lead Drug Discovery)
Protein–protein interactions (PPIs) represent an extremely attractive class of potential new targets for therapeutic intervention; however, the shallow extended character of many PPIs can render developing inhibitors against them as exceptionally difficult. Yet this problem can be made tractable by taking advantage of the fact that large interacting surfaces are often characterized by confined “hot spot” regions, where interactions contribute disproportionately to overall binding energies. Peptides afford valuable starting points for developing PPI inhibitors because of their high degrees of functional diversity and conformational adaptability. Unfortunately, contacts afforded by the 20 natural amino acids may be suboptimal and inefficient for accessing both canonical binding interactions and transient “cryptic” binding pockets. Oxime ligation represents a class of biocompatible “click” chemistry that allows the structural diversity of libraries of aldehydes to be rapidly evaluated within the context of a parent oxime-containing peptide platform. Importantly, oxime ligation represents a form of post solid-phase diversification, which provides a facile and empirical means of identifying unanticipated protein–peptide interactions that may substantially increase binding affinities and selectivity. The current review will focus on the authors’ use of peptide ligation to optimize PPI antagonists directed against several targets, including tumor susceptibility gene 101 (Tsg101), protein tyrosine phosphatases (PTPases) and the polo-like kinase 1 (Plk1). This should provide insights that can be broadly directed against an almost unlimited range of physiologically important PPIs. View Full-Text
Keywords: peptidomimetics; peptide oxime ligation; tethered fragment libraries; protein–protein interactions (PPIs); post solid-phase diversification peptidomimetics; peptide oxime ligation; tethered fragment libraries; protein–protein interactions (PPIs); post solid-phase diversification
Show Figures

Graphical abstract

MDPI and ACS Style

Zhao, X.Z.; Liu, F.; Burke, T.R., Jr. Application of Post Solid-Phase Oxime Ligation to Fine-Tune Peptide–Protein Interactions. Molecules 2020, 25, 2807. https://doi.org/10.3390/molecules25122807

AMA Style

Zhao XZ, Liu F, Burke TR Jr. Application of Post Solid-Phase Oxime Ligation to Fine-Tune Peptide–Protein Interactions. Molecules. 2020; 25(12):2807. https://doi.org/10.3390/molecules25122807

Chicago/Turabian Style

Zhao, Xue Zhi, Fa Liu, and Terrence R. Burke Jr. 2020. "Application of Post Solid-Phase Oxime Ligation to Fine-Tune Peptide–Protein Interactions" Molecules 25, no. 12: 2807. https://doi.org/10.3390/molecules25122807

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop