publication . Article . 2016

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; ...
Open Access English
  • Published: 21 Jan 2016 Journal: Scientific Reports, volume 6, pages 19431-1-19431-12 (issn: 2045-2322, eissn: 2045-2322, Copyright policy)
  • Publisher: Nature Publishing Group
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 extensiv...
Subjects
free text keywords: Article

hTis work was supported by the Medical Research Council (Grant MR/K000179/1 to A.M.B.), the Ministry of Education of the Czech Republic (Grants LK11205 and LO1304 to V.V.), and Research Project RVO:61388963 of the Czech Academy of Sciences (to the Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences). We thank Diamond Light Source for access their beamlines (proposal number mx-7864) that contributed to the results presented here.

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 extensiv...
Subjects
free text keywords: Article

hTis work was supported by the Medical Research Council (Grant MR/K000179/1 to A.M.B.), the Ministry of Education of the Czech Republic (Grants LK11205 and LO1304 to V.V.), and Research Project RVO:61388963 of the Czech Academy of Sciences (to the Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences). We thank Diamond Light Source for access their beamlines (proposal number mx-7864) that contributed to the results presented here.

Powered by OpenAIRE Open Research Graph
Any information missing or wrong?Report an Issue
publication . Article . 2016

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; ...