The effect of peptide size on target affinity in mRNA display-derived macrocyclic peptides

Xuefei Jing; Jen Suh; Joshua Maxwell; Karishma Patel; Alexander Norman; Xavier J. Reid; Chandrika Deshpande; Jason K. K. Low; Richard J. Payne; Toby Passioura; Joel P. Mackay

doi:10.1039/D5CC06167A

The effect of peptide size on target affinity in mRNA display-derived macrocyclic peptides

Xuefei Jing,

^a Jen Suh,^a Joshua Maxwell,^b Karishma Patel,^a Alexander Norman,^b Xavier J. Reid,^a Chandrika Deshpande,^a Jason K. K. Low,^a Richard J. Payne,

^b Toby Passioura

*^bc and Joel P. Mackay

*^a

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* Corresponding authors

^a School of Life and Environmental Sciences, University of Sydney, NSW 2006, Australia
E-mail: joel.mackay@sydney.edu.au

^b School of Chemistry, University of Sydney, NSW 2006, Australia
E-mail: toby@insamo.com

^c Insamo South Pty Ltd, Chippendale, NSW, Australia

Abstract

The large size of macrocyclic peptides discovered by mRNA display can hinder therapeutic development. Using size-restricted RaPID libraries and analysis of 40 published datasets, we show that potent binders are more reliably identified from libraries with at least nine randomised residues, providing guidance for mRNA display screen design.

Chemical Communications

The effect of peptide size on target affinity in mRNA display-derived macrocyclic peptides

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The effect of peptide size on target affinity in mRNA display-derived macrocyclic peptides

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