Publications by authors named "Nicolas A Abrigo"

A key limitation for the development of peptides as therapeutics is their lack of cell permeability. Recent work has shown that short, arginine-rich macrocyclic peptides containing hydrophobic amino acids are able to penetrate cells and reach the cytosol. Here, we have developed a new strategy for developing cyclic cell penetrating peptides (CPPs) that shifts some of the hydrophobic character to the peptide cyclization linker, allowing us to do a linker screen to find cyclic CPPs with improved cellular uptake.

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Article Synopsis
  • Peptide macrocyclization enhances the development of more effective and stable protein ligands, making it crucial in peptide drug discovery.
  • The study involved creating a diverse peptide library with different ring sizes and shapes (monocyclic, bicyclic, and linear) through mRNA display, followed by in vitro selection against streptavidin.
  • The analysis revealed valuable insights into the binding affinities of different peptide topologies and their performance under protease challenges, contributing to our understanding of peptide diversity in drug discovery.
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Article Synopsis
  • Hydrocarbon stapled peptides are potential drugs that can block interactions between proteins inside cells.
  • A new method using mRNA display is created to quickly discover these stapled peptides, utilizing α-methyl cysteine and m-dibromoxylene for cyclization.
  • The research specifically aims to find a peptide that can effectively bind to the HPV16 E2 protein, which is relevant for HPV-related diseases.
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The ability to introduce non-canonical amino acids into peptides and proteins is facilitated by working within in vitro translation systems. Non-canonical amino acids can be introduced into these systems using sense codon reprogramming, stop codon suppression, and by breaking codon degeneracy. Here, we review how these techniques have been used to create proteins with novel properties and how they facilitate sophisticated studies of protein function.

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