By the same authors

From the same journal

From the same journal

Rational steering of insulin binding specificity by intra-chain chemical crosslinking

Research output: Contribution to journalArticlepeer-review

Full text download(s)

Published copy (DOI)


  • Jitka Viková
  • Michaela Collinsová
  • Emília Kletvíková
  • Miloš Budšínský
  • Lenka Záková
  • Václav Veverka
  • Rozálie Hexnerová
  • Roberto J Tarazona Aviñó
  • Jana Straková
  • Irena Selicharová
  • Václav Vank
  • Daniel W. Wright
  • Christopher J. Watson
  • Johan P. Turkenburg
  • Andrzej M. Brzozowski
  • Jí Jiráek


Publication details

JournalScientific Reports
DateAccepted/In press - 11 Dec 2015
DatePublished (current) - 21 Jan 2016
Number of pages12
Original languageEnglish


Insulin is a key hormone of human metabolism with major therapeutic importance for both types of diabetes. New insulin analogues with more physiological profiles and better glycemic control are needed, especially analogues that preferentially bind to the metabolic B-isoform of insulin receptor (IR-B). Here, we aimed to stabilize and modulate the receptor-compatible conformation of insulin by covalent intra-chain crosslinking within its B22-B30 segment, using the Cu I -catalyzed Huisgen 1,3-dipolar cycloaddition reaction of azides and alkynes. This approach resulted in 14 new, systematically crosslinked insulin analogues whose structures and functions were extensively characterized and correlated. One of the analogues, containing a B26-B29 triazole bridge, was highly active in binding to both IR isoforms, with a significant preference for IR-B. Our results demonstrate the potential of chemistry-driven modulation of insulin function, also shedding new light on the functional importance of hormones B-chain C-terminus for its IR-B specificity.

Bibliographical note

This content is made available by the publisher under a Creative Commons Attribution Licence. This means that a user may copy, distribute and display the resource providing that they give credit. Users must adhere to the terms of the licence.

Discover related content

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

View graph of relations