Rational steering of insulin binding specificity by intra-chain chemical crosslinking
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F16%3A00458657" target="_blank" >RIV/61388963:_____/16:00458657 - isvavai.cz</a>
Result on the web
<a href="http://www.nature.com/articles/srep19431" target="_blank" >http://www.nature.com/articles/srep19431</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/srep19431" target="_blank" >10.1038/srep19431</a>
Alternative languages
Result language
angličtina
Original language name
Rational steering of insulin binding specificity by intra-chain chemical crosslinking
Original language description
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 hormone's B-chain C-terminus for its IR-B specificity.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
CE - Biochemistry
OECD FORD branch
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Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Scientific Reports
ISSN
2045-2322
e-ISSN
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Volume of the periodical
6
Issue of the periodical within the volume
Jan 21
Country of publishing house
GB - UNITED KINGDOM
Number of pages
12
Pages from-to
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UT code for WoS article
000368775800001
EID of the result in the Scopus database
2-s2.0-84955617718