By the same authors

From the same journal

Insulin-like Growth Factor 1 Analogs Clicked in the C Domain: Chemical Synthesis and Biological Activities

Research output: Contribution to journalArticlepeer-review

Full text download(s)

Published copy (DOI)


  • Kateřina Macháčková
  • Michaela Collinsová
  • Martina Chrudinová
  • Irena Selicharová
  • Jan Pícha
  • Miloš Buděšínský
  • Václav Vaněk
  • Lenka Žáková
  • Andrzej M. Brzozowski
  • Jiří Jiráček


Publication details

DateE-pub ahead of print - 27 Nov 2017
DatePublished (current) - 28 Dec 2017
Issue number24
Number of pages13
Pages (from-to)10105-10117
Early online date27/11/17
Original languageEnglish


Human insulin-like growth factor 1 (IGF-1) is a 70 amino acid protein hormone, with key impact on growth, development, and lifespan. The physiological and clinical importance of IGF-1 prompted challenging chemical and biological trials toward the development of its analogs as molecular tools for the IGF-1 receptor (IGF1-R) studies and as new therapeutics. Here, we report a new method for the total chemical synthesis of IGF-1 analogs, which entails the solid-phase synthesis of two IGF-1 precursor chains that is followed by the CuI-catalyzed azide-alkyne cycloaddition ligation and by biomimetic formation of a native pattern of disulfides. The connection of the two IGF-1 precursor chains by the triazole-containing moieties, and variation of its neighboring sequences (Arg36 and Arg37), was tolerated in IGF-1R binding and its activation. These new synthetic IGF-1 analogs are unique examples of disulfide bonds' rich proteins with intra main-chain triazole links. The methodology reported here also presents a convenient synthetic platform for the design and production of new analogs of this important human hormone with non-standard protein modifications.

Bibliographical note

© 2017 American Chemical Society.

Discover related content

Find related publications, people, projects, datasets and more using interactive charts.

View graph of relations