Biocompatible macrocyclization between cysteine and 2-cyanopyridine generates stable peptide inhibitors

Biocompatible macrocyclization between cysteine and 2-cyanopyridine generates stable peptide inhibitors

Peptides featuring an N-terminal cysteine residue and the unnatural amino acid 3-(2-cyano-4-pyridyl)alanine (Cpa) cyclize spontaneously in aqueous solution at neutral pH. Cpa is readily available and easily introduced into peptides using standard solid-phase peptide synthesis. The reaction is orthog...

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Main Authors: Nitsche, Christoph, Onagi, Hideki, Quek, Jun-Ping, Otting, Gottfried, Luo, Dahai, Huber, Thomas
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2020
Subjects:
Science::Medicine
Peptides and Proteins
Monomers
Online Access:https://hdl.handle.net/10356/140796
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1407962020-11-01T05:21:47Z Biocompatible macrocyclization between cysteine and 2-cyanopyridine generates stable peptide inhibitors Nitsche, Christoph Onagi, Hideki Quek, Jun-Ping Otting, Gottfried Luo, Dahai Huber, Thomas Lee Kong Chian School of Medicine (LKCMedicine) Science::Medicine Peptides and Proteins Monomers Peptides featuring an N-terminal cysteine residue and the unnatural amino acid 3-(2-cyano-4-pyridyl)alanine (Cpa) cyclize spontaneously in aqueous solution at neutral pH. Cpa is readily available and easily introduced into peptides using standard solid-phase peptide synthesis. The reaction is orthogonal to all proteinogenic amino acids, including cysteine residues that are not at the N-terminus. A substrate peptide of the Zika virus NS2B-NS3 protease cyclized in this way produced an inhibitor of high affinity and proteolytic stability. NRF (Natl Research Foundation, S’pore) Accepted version 2020-06-02T04:05:36Z 2020-06-02T04:05:36Z 2019 Journal Article Nitsche, C., Onagi, H., Quek, J.-P., Otting, G., Luo, D., & Huber, T. (2019). Biocompatible macrocyclization between cysteine and 2-cyanopyridine generates stable peptide inhibitors. Organic Letters, 21(12), 4709-4712. doi:10.1021/acs.orglett.9b01545 1523-7060 https://hdl.handle.net/10356/140796 10.1021/acs.orglett.9b01545 31188009 2-s2.0-85067638559 12 21 4709 4712 en Organic Letters This document is the Accepted Manuscript version of a Published Work that appeared in final form in Organic Letters, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.orglett.9b01545 application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
Peptides and Proteins
Monomers
spellingShingle Science::Medicine
Peptides and Proteins
Monomers
Nitsche, Christoph
Onagi, Hideki
Quek, Jun-Ping
Otting, Gottfried
Luo, Dahai
Huber, Thomas
Biocompatible macrocyclization between cysteine and 2-cyanopyridine generates stable peptide inhibitors
description Peptides featuring an N-terminal cysteine residue and the unnatural amino acid 3-(2-cyano-4-pyridyl)alanine (Cpa) cyclize spontaneously in aqueous solution at neutral pH. Cpa is readily available and easily introduced into peptides using standard solid-phase peptide synthesis. The reaction is orthogonal to all proteinogenic amino acids, including cysteine residues that are not at the N-terminus. A substrate peptide of the Zika virus NS2B-NS3 protease cyclized in this way produced an inhibitor of high affinity and proteolytic stability.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Nitsche, Christoph
Onagi, Hideki
Quek, Jun-Ping
Otting, Gottfried
Luo, Dahai
Huber, Thomas
format Article
author Nitsche, Christoph
Onagi, Hideki
Quek, Jun-Ping
Otting, Gottfried
Luo, Dahai
Huber, Thomas
author_sort Nitsche, Christoph
title Biocompatible macrocyclization between cysteine and 2-cyanopyridine generates stable peptide inhibitors
title_short Biocompatible macrocyclization between cysteine and 2-cyanopyridine generates stable peptide inhibitors
title_full Biocompatible macrocyclization between cysteine and 2-cyanopyridine generates stable peptide inhibitors
title_fullStr Biocompatible macrocyclization between cysteine and 2-cyanopyridine generates stable peptide inhibitors
title_full_unstemmed Biocompatible macrocyclization between cysteine and 2-cyanopyridine generates stable peptide inhibitors
title_sort biocompatible macrocyclization between cysteine and 2-cyanopyridine generates stable peptide inhibitors
publishDate 2020
url https://hdl.handle.net/10356/140796
_version_ 1683493823356862464

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