-
Je něco špatně v tomto záznamu ?
Targeting the insulin receptor with hormone and peptide dimers
J. Lin, I. Selicharová, K. Mitrová, B. Fabre, VM. Miriyala, M. Lepšík, J. Jiráček, MSG. Hernández
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články
Grantová podpora
MR/R009066/1
Medical Research Council - United Kingdom
PubMed
36336650
DOI
10.1002/psc.3461
Knihovny.cz E-zdroje
- MeSH
- inzulin metabolismus MeSH
- lidé MeSH
- peptidy * chemie MeSH
- polyethylenglykoly MeSH
- protein - isoformy MeSH
- receptor inzulinu * metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Insulin is a key hormone involved in the regulation of overall energetic homeostasis of the organism. The dimeric character of the receptor for insulin evokes ideas about its activation or inhibition with peptide dimers that could either trigger or block the structural transition of the insulin receptor, leading to its activation. Herewith, we present the chemical engineering and biological characterization of several series of insulin dimers or dimers of specific peptides that should be able to bind receptors for insulin or insulin growth factor 1. The hormones or peptides in the dimers were interconnected with different linkers, consisting of triazole moieties and 3, 6, 8, 11, or 23 polyethylene glycol units. The prepared dimers were weaker in binding to insulin receptors than human insulin. However, some of the insulin dimers showed preferential binding specificity toward the isoform A of the insulin receptor, and the insulin dimers also stimulated the insulin receptor more strongly than would be consistent with their binding affinities. Our results suggest that designing insulin dimers may be a promising strategy for modulating the ability of the hormone to activate the receptor or to alter its specificity toward insulin receptor isoforms.
Department of Biochemistry Faculty of Science Charles University Prague Czech Republic
Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Prague Czech Republic
- 000
- 00000naa a2200000 a 4500
- 001
- bmc23003719
- 003
- CZ-PrNML
- 005
- 20230425140828.0
- 007
- ta
- 008
- 230418s2023 enk f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1002/psc.3461 $2 doi
- 035 __
- $a (PubMed)36336650
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a enk
- 100 1_
- $a Lin, Jingjing $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic $u Department of Biochemistry, Faculty of Science, Charles University, Prague, Czech Republic
- 245 10
- $a Targeting the insulin receptor with hormone and peptide dimers / $c J. Lin, I. Selicharová, K. Mitrová, B. Fabre, VM. Miriyala, M. Lepšík, J. Jiráček, MSG. Hernández
- 520 9_
- $a Insulin is a key hormone involved in the regulation of overall energetic homeostasis of the organism. The dimeric character of the receptor for insulin evokes ideas about its activation or inhibition with peptide dimers that could either trigger or block the structural transition of the insulin receptor, leading to its activation. Herewith, we present the chemical engineering and biological characterization of several series of insulin dimers or dimers of specific peptides that should be able to bind receptors for insulin or insulin growth factor 1. The hormones or peptides in the dimers were interconnected with different linkers, consisting of triazole moieties and 3, 6, 8, 11, or 23 polyethylene glycol units. The prepared dimers were weaker in binding to insulin receptors than human insulin. However, some of the insulin dimers showed preferential binding specificity toward the isoform A of the insulin receptor, and the insulin dimers also stimulated the insulin receptor more strongly than would be consistent with their binding affinities. Our results suggest that designing insulin dimers may be a promising strategy for modulating the ability of the hormone to activate the receptor or to alter its specificity toward insulin receptor isoforms.
- 650 _2
- $a lidé $7 D006801
- 650 12
- $a receptor inzulinu $x metabolismus $7 D011972
- 650 12
- $a peptidy $x chemie $7 D010455
- 650 _2
- $a inzulin $x metabolismus $7 D007328
- 650 _2
- $a protein - isoformy $7 D020033
- 650 _2
- $a polyethylenglykoly $7 D011092
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Selicharová, Irena $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic
- 700 1_
- $a Mitrová, Katarína $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic
- 700 1_
- $a Fabre, Benjamin $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic
- 700 1_
- $a Miriyala, Vijay Madhav $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic $u Regional Center of Advanced Technologies and Materials, Czech Advanced Technology and Research Institute, Palacký University Olomouc, Olomouc, Czech Republic
- 700 1_
- $a Lepšík, Martin $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic
- 700 1_
- $a Jiráček, Jiří $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic $1 https://orcid.org/0000000338482773 $7 xx0098873
- 700 1_
- $a Hernández, María Soledad Garre $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic $1 https://orcid.org/0000000270753548
- 773 0_
- $w MED00002886 $t Journal of peptide science : an official publication of the European Peptide Society $x 1099-1387 $g Roč. 29, č. 4 (2023), s. e3461
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/36336650 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y p $z 0
- 990 __
- $a 20230418 $b ABA008
- 991 __
- $a 20230425140824 $b ABA008
- 999 __
- $a ok $b bmc $g 1924410 $s 1189928
- BAS __
- $a 3
- BAS __
- $a PreBMC-MEDLINE
- BMC __
- $a 2023 $b 29 $c 4 $d e3461 $e 20221114 $i 1099-1387 $m Journal of peptide science $n J Pept Sci $x MED00002886
- GRA __
- $a MR/R009066/1 $p Medical Research Council $2 United Kingdom
- LZP __
- $a Pubmed-20230418