Insulin Analogues with Altered Insulin Receptor Isoform Binding Specificities and Enhanced Aggregation Stabilities
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22330%2F21%3A43934148" target="_blank" >RIV/60461373:22330/21:43934148 - isvavai.cz</a>
Alternative codes found
RIV/61388963:_____/21:00546413
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acs.jmedchem.1c01388" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jmedchem.1c01388</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jmedchem.1c01388" target="_blank" >10.1021/acs.jmedchem.1c01388</a>
Alternative languages
Result language
angličtina
Original language name
Insulin Analogues with Altered Insulin Receptor Isoform Binding Specificities and Enhanced Aggregation Stabilities
Original language description
Insulin is a lifesaver for millions of diabetic patients. There is a need for new insulin analogues with more physiological profiles and analogues that will be thermally more stable than human insulin. Here, we describe the chemical engineering of 48 insulin analogues that were designed to have changed binding specificities toward isoforms A and B of the insulin receptor (IR-A and IR-B). We systematically modified insulin at the C-terminus of the B-chain, at the N-terminus of the A-chain, and at A14 and A18 positions. We discovered an insulin analogue that has Cα-carboxyamidated Glu at B31 and Ala at B29 and that has a more than 3-fold-enhanced binding specificity in favor of the "metabolic"IR-B isoform. The analogue is more resistant to the formation of insulin fibrils at 37 °C and is also more efficient in mice than human insulin. Therefore, [AlaB29,GluB31,amideB31]-insulin may be interesting for further clinical evaluation. © 2021 American Chemical Society.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30100 - Basic medicine
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
JOURNAL OF MEDICINAL CHEMISTRY
ISSN
0022-2623
e-ISSN
1520-4804
Volume of the periodical
64
Issue of the periodical within the volume
19
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
14848-14859
UT code for WoS article
000709633100048
EID of the result in the Scopus database
2-s2.0-85117073608