In Vitro Selection of Macrocyclic α/β-Peptides Against Human EGFR

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2022 Sep 29

PMID 36173923

Authors

Risa Wakabayashi

Marina Kawai

Takayuki Katoh

Hiroaki Suga

Affiliations

Soon will be listed here.

Abstract

Here, we report ribosomal construction of thioether-macrocyclic α/β-peptide libraries in which β-homoglycine, β-homoalanine, β-homophenylglycine, and β-homoglutamine are introduced by genetic code reprogramming. The libraries were applied to the RaPID (Random nonstandard Peptides Integrated Discovery) selection against human EGFR to obtain PPI (protein-protein interaction) inhibitors. The resulting peptides contained up to five β-amino acid (βAA) residues and exhibited outstanding binding affinity, PPI inhibitory activity, and proteolytic stability, which were attributed to the βAAs included in the peptides. This showcase work has demonstrated that the use of such βAAs enhances the drug-like properties of peptides, providing a unique platform for the discovery of de novo macrocycles against a protein of interest.

Citing Articles

Reprogramming the genetic code with flexizymes.

Katoh T, Suga H Nat Rev Chem. 2024; 8(12):879-892.

PMID: 39433956 DOI: 10.1038/s41570-024-00656-5.

In Vitro Selection of Macrocyclic l-α/d-α/β/γ-Hybrid Peptides Targeting IFN-γ/IFNGR1 Protein-Protein Interaction.

Miura T, Lee K, Katoh T, Suga H J Am Chem Soc. 2024; 146(26):17691-17699.

PMID: 38888290 PMC: 11229689. DOI: 10.1021/jacs.4c01979.

Engineering tRNAs for the Ribosomal Translation of Non-proteinogenic Monomers.

Sigal M, Matsumoto S, Beattie A, Katoh T, Suga H Chem Rev. 2024; 124(10):6444-6500.

PMID: 38688034 PMC: 11122139. DOI: 10.1021/acs.chemrev.3c00894.

Fine-tuning the tRNA anticodon arm for multiple/consecutive incorporations of β-amino acids and analogs.

Katoh T, Suga H Nucleic Acids Res. 2024; 52(11):6586-6595.

PMID: 38572748 PMC: 11194099. DOI: 10.1093/nar/gkae219.

References

Katoh T, Iwane Y, Suga H . Logical engineering of D-arm and T-stem of tRNA that enhances d-amino acid incorporation. Nucleic Acids Res. 2017; 45(22):12601-12610. PMC: 5728406. DOI: 10.1093/nar/gkx1129. View

Katoh T, Wohlgemuth I, Nagano M, Rodnina M, Suga H . Essential structural elements in tRNA(Pro) for EF-P-mediated alleviation of translation stalling. Nat Commun. 2016; 7:11657. PMC: 4890201. DOI: 10.1038/ncomms11657. View

Hill D, Mio M, Prince R, Hughes T, Moore J . A field guide to foldamers. Chem Rev. 2001; 101(12):3893-4012. DOI: 10.1021/cr990120t. View

Loong H, Kwan S, Mok T, Lau Y . Therapeutic Strategies in EGFR Mutant Non-Small Cell Lung Cancer. Curr Treat Options Oncol. 2018; 19(11):58. DOI: 10.1007/s11864-018-0570-9. View

Bielefeld-Sevigny M . AlphaLISA immunoassay platform- the "no-wash" high-throughput alternative to ELISA. Assay Drug Dev Technol. 2009; 7(1):90-2. DOI: 10.1089/adt.2009.9996. View

Yamagishi Y, Shoji I, Miyagawa S, Kawakami T, Katoh T, Goto Y . Natural product-like macrocyclic N-methyl-peptide inhibitors against a ubiquitin ligase uncovered from a ribosome-expressed de novo library. Chem Biol. 2011; 18(12):1562-70. DOI: 10.1016/j.chembiol.2011.09.013. View

Gopi H, Ravindra G, Pal P, Pattanaik P, Balaram H, Balaram P . Proteolytic stability of beta-peptide bonds probed using quenched fluorescent substrates incorporating a hemoglobin cleavage site. FEBS Lett. 2003; 535(1-3):175-8. DOI: 10.1016/s0014-5793(02)03885-1. View

Strijowski U, Sewald N . Structural properties of cyclic peptides containing cis- or trans-2-aminocyclohexane carboxylic acid. Org Biomol Chem. 2004; 2(8):1105-9. DOI: 10.1039/b312432k. View

Imanishi S, Katoh T, Yin Y, Yamada M, Kawai M, Suga H . In Vitro Selection of Macrocyclic d/l-Hybrid Peptides against Human EGFR. J Am Chem Soc. 2021; 143(15):5680-5684. DOI: 10.1021/jacs.1c02593. View

10.

Czekster C, Robertson W, Walker A, Soll D, Schepartz A . In Vivo Biosynthesis of a β-Amino Acid-Containing Protein. J Am Chem Soc. 2016; 138(16):5194-7. PMC: 6640638. DOI: 10.1021/jacs.6b01023. View

11.

Maini R, Nguyen D, Chen S, Dedkova L, Roy Chowdhury S, Alcala-Torano R . Incorporation of β-amino acids into dihydrofolate reductase by ribosomes having modifications in the peptidyltransferase center. Bioorg Med Chem. 2013; 21(5):1088-96. DOI: 10.1016/j.bmc.2013.01.002. View

12.

Guthohrlein E, Malesevic M, Majer Z, Sewald N . Secondary structure inducing potential of beta-amino acids: torsion angle clustering facilitates comparison and analysis of the conformation during MD trajectories. Biopolymers. 2007; 88(6):829-39. DOI: 10.1002/bip.20859. View

13.

Choi S, Guzei I, Spencer L, Gellman S . Crystallographic characterization of helical secondary structures in alpha/beta-peptides with 1:1 residue alternation. J Am Chem Soc. 2008; 130(20):6544-50. DOI: 10.1021/ja800355p. View

14.

Hook D, Bindschadler P, Mahajan Y, Sebesta R, Kast P, Seebach D . The proteolytic stability of 'designed' beta-peptides containing alpha-peptide-bond mimics and of mixed alpha,beta-peptides: application to the construction of MHC-binding peptides. Chem Biodivers. 2006; 2(5):591-632. DOI: 10.1002/cbdv.200590039. View

15.

Aguilar M, Purcell A, Devi R, Lew R, Rossjohn J, Smith A . Beta-amino acid-containing hybrid peptides--new opportunities in peptidomimetics. Org Biomol Chem. 2007; 5(18):2884-90. DOI: 10.1039/b708507a. View

16.

Yasgar A, Jadhav A, Simeonov A, Coussens N . AlphaScreen-Based Assays: Ultra-High-Throughput Screening for Small-Molecule Inhibitors of Challenging Enzymes and Protein-Protein Interactions. Methods Mol Biol. 2016; 1439:77-98. PMC: 5444910. DOI: 10.1007/978-1-4939-3673-1_5. View

17.

Appella D, Christianson L, Klein D, Powell D, Huang X, Barchi Jr J . Residue-based control of helix shape in beta-peptide oligomers. Nature. 1997; 387(6631):381-4. DOI: 10.1038/387381a0. View

18.

Maini R, Roy Chowdhury S, Dedkova L, Roy B, Daskalova S, Paul R . Protein Synthesis with Ribosomes Selected for the Incorporation of β-Amino Acids. Biochemistry. 2015; 54(23):3694-706. PMC: 4472090. DOI: 10.1021/acs.biochem.5b00389. View

19.

Katoh T, Sengoku T, Hirata K, Ogata K, Suga H . Ribosomal synthesis and de novo discovery of bioactive foldamer peptides containing cyclic β-amino acids. Nat Chem. 2020; 12(11):1081-1088. DOI: 10.1038/s41557-020-0525-1. View

20.

Goto Y, Ohta A, Sako Y, Yamagishi Y, Murakami H, Suga H . Reprogramming the translation initiation for the synthesis of physiologically stable cyclic peptides. ACS Chem Biol. 2008; 3(2):120-9. DOI: 10.1021/cb700233t. View