Diamond Publications - Search Results

Search Again...

These results only include publications that have been reviewed and processed by Diamond Light Source. To also view papers that have not yet been processed click here.

You can use the folder icon under Actions to collate papers as required. You can then click on View Folder in the left-hand navigation to review and/or download your folder.

One item found (0 items not approved).

Instruments / Technical Area	Publication Details	Published	Actions
I03-Macromolecular Crystallography	Rational steering of insulin binding specificity by intra-chain chemical crosslinking Jitka Viková , Michaela Collinsová , Emília Kletvíková , Miloš Buděšínský , Vojtěch Kaplan , Lenka Žáková , Václav Veverka , Rozálie Hexnerová , Roberto J. Tarazona Aviñó , Jana Straková , Irena Selicharová , Václav Vaněk , Daniel W Wright , Christopher J Watson , Johan P Turkenburg , Andrzej M Brzozowski , Jiří Jiráček Scientific Reports 6 DOI: 10.1038/srep19431 PMID: 26792393 Diamond Proposal Number(s): [7864] Open Access Show Abstract ▼ Abstract: 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 CuI-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 hormone’s B-chain C-terminus for its IR-B specificity.	Jan 2016

Instruments / Technical Area

Publication Details

Published

Actions

I03-Macromolecular Crystallography

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