# Reprogramming RiPP scaffolds through skeletal editing unlocks chemical space

https://mdr.nims.go.jp/datasets/dcb95d8c-242f-4dd3-b0ab-bb1dcb67d6e9

## File

- [d6sc03088b.pdf](https://mdr.nims.go.jp/filesets/ea03e11d-c968-4fea-bcf3-2d3163f23989/download) ([Detail](https://mdr.nims.go.jp/filesets/ea03e11d-c968-4fea-bcf3-2d3163f23989.md))

## Id

dcb95d8c-242f-4dd3-b0ab-bb1dcb67d6e9

## Local identifier



## Visibility

open_to_public

## State

published

## Created at

2026-11-02T05:01:51.272830Z

## Updated at

2026-11-02T05:32:55.438452Z

## Published at

2026-11-02T07:34:13.594952Z

## Doi



## First published url

https://doi.org/10.1039/d6sc03088b

## Date published

2026-05-26

## Recorded date published

2026-7-22

## Resource type

journal_article

## Manuscript type

vor

## Collection



## Title

- title: Reprogramming RiPP scaffolds through skeletal editing unlocks chemical space
  title_type: original
  lang: en

## Description

- description: In this study, we report (1) a scalable, systematic, and general synthetic
    approach for the supply of ribosomally synthesized and post-translationally modified
    peptides (RiPPs) bearing Tyr–Trp cross-linkages, and (2) the comprehensive expansion
    of novel chemical space through their skeletal diversification. In recent years,
    numerous biaryl-containing peptides have been discovered, and some of these RiPPs
    exhibit potent biological activities. However, despite the high metabolic stability
    and strong target protein binding generally attributed to biaryl RiPPs, their
    significant strain and rigidity have limited the availability of general synthetic
    methods. Here, we demonstrate the high versatility of modular synthetic strategies
    for the construction of RiPPs and achieve the synthesis of a variety of RiPPs
    containing Tyr–Trp cross-linkages. Furthermore, skeletal diversification via scaffold
    hopping enables access to artificial RiPP scaffolds incorporating quinazoline
    and quinoline motifs, whose preparation has previously been challenging.
  description_type: abstract
  lang: und

## Creator

- name: Hiroshige Ogawa
  role: author
- name: Longhui Yu
  role: author
- name: Shangzhao Li
  role: author
- name: Yuuya Nagata
  role: author
  orcid: https://orcid.org/0000-0001-5926-5845
  organization: National Institute for Materials Science
- name: Tsz Ki Chan
  role: author
- name: Yudai Matsuda
  role: author
- name: Jing Liu
  role: author
- name: Yong-Xin Li
  role: author
- name: Hugh Nakamura
  role: author

## Contact agent



## Publisher

organization: Royal Society of Chemistry (RSC)

## Managing organization



## Keyword

- subject: Ribosomally Synthesized and Post-translationally Modified Peptides
  schema: not_defined
- subject: Skeletal Editing
  schema: not_defined
- subject: Scaffold Hopping
  schema: not_defined
- subject: Larock Macrocyclization
  schema: not_defined
- subject: C–H Arylation
  schema: not_defined

## Rights

- identifier: https://creativecommons.org/licenses/by/4.0/
  date_licensed: 2026-05-26

## Other identifier(s)



## Data origin

- data_origin_type: other

## Embargo



## Journal

- title: Chemical Science
  issn: '20416520'
  volume: '17'
  issue: '28'
  start_page: 13835
  end_page: 13849

## Conference



## Related item



## Funding

- identifier: NSFC25SC26
  funder_name: National Natural Science Foundation of China
- identifier: '26302024'
  funder_name: Research Grants Council, University Grants Committee
- identifier: '16306525'
  funder_name: Research Grants Council, University Grants Committee
- identifier: R9820
  funder_name: Hong Kong University of Science and Technology
- identifier: JP23H03810
  funder_name: Japan Society for the Promotion of Science
- identifier: JPMJER1903
  funder_name: Japan Science and Technology Corporation
- identifier: '7020157'
  funder_name: Shenzhen Research Institute, City University of Hong Kong

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## Specimen



## Chemical composition



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## Fileset

- id: ea03e11d-c968-4fea-bcf3-2d3163f23989
  filename: d6sc03088b.pdf
  content_type: application/pdf
  size: 5905779
  md5: 69a098b1d4dd98a81498a99a804b0040

## Thumbnail

fileset_id: ea03e11d-c968-4fea-bcf3-2d3163f23989
filename: d6sc03088b.pdf