Studies on monomeric insulin with reduced self-association are important in the development of insulin pharmaceutical preparations with rapid hypoglycemic action on patients with diabetes. Here we report a novel monomeric insulin, B22 Glu des-B30 insulin, prepared from a single chain insulin precursor with B22 Arg mutated to Glu, which was expressed in Pichia pastoris and converted to B22 Glu des-B30 insulin by tryptic digestion. It still retains 50% of the in vivo biological activity of porcine insulin and does not form a dimer even at a concentration of 10 mg/ml, showing that B22 Glu plays a key role in reducing the self-association of the insulin molecule without greatly reducing its biological activity. This novel monomeric insulin might have potential applications in the clinic.
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http://dx.doi.org/10.1111/j.1745-7270.2006.00198.x | DOI Listing |
Hum Genome Var
May 2023
Department of Medical Genetics and Pathology, Ardabil University of Medical Sciences, Ardabil, Iran.
A 30-year-old male couple from Ardabil city, Iran, were admitted for premarital screening. An abnormal band in HbS/D regions with high levels of HbF and HbA 2 led us to suspect the possibility of a compound heterozygous state of β-thalassemia in our affected proband. Therefore, beta globin chain sequencing of proband discovered a heterozygote combination of the Hb G-Coushatta [b22 (B4) Glu>Ala, HBB: c.
View Article and Find Full Text PDFArch Biochem Biophys
June 2022
Razi Vaccine and Serum Research Institute, Agriculture Research, Education and Extension Organization (AREEO), Mashhad, Iran.
Copper nanoparticles with different sizes cause significant changes in humans, and their interaction with biological molecules such as proteins is one of molecular biology's most critical and difficult challenges. One of the valuable tools for understating the mechanisms of different protein-nanoparticle interactions are molecular dynamics simulations. The present work attempts to understand how insulin interaction mechanisms Cu nanoparticles of different sizes (2, 6, and 10 nm) may occur with the molecular dynamics simulations methods.
View Article and Find Full Text PDFJ Biotechnol
December 2015
Genetics and Physiology of Microalgae, Institute of Botany, B22, University of Liège, Belgium. Electronic address:
Biomass composition of Chlamydomonas reinhardtii was studied during two consecutive cycles of 12h light/12h dark. As in our experimental conditions the two synchronized divisions were separated by 20h, it was possible to show that accumulation of dry weight, proteins, chlorophyll and fatty acids mainly depends on cell division, whereas starch accumulation depends on a circadian rhythm as reported previously. Our metabolomics analyses also revealed that accumulation of five (Ser, Val, Leu, Ile and Thr) of the nine free amino acids detected displayed rhythmicity, depending on cell division while Glu was 20-50 times more abundant than the other ones probably because this free amino acid serves not only for protein synthesis but also for biosynthesis of nitrogen compounds.
View Article and Find Full Text PDFActa Biochim Biophys Sin (Shanghai)
August 2006
Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Studies on monomeric insulin with reduced self-association are important in the development of insulin pharmaceutical preparations with rapid hypoglycemic action on patients with diabetes. Here we report a novel monomeric insulin, B22 Glu des-B30 insulin, prepared from a single chain insulin precursor with B22 Arg mutated to Glu, which was expressed in Pichia pastoris and converted to B22 Glu des-B30 insulin by tryptic digestion. It still retains 50% of the in vivo biological activity of porcine insulin and does not form a dimer even at a concentration of 10 mg/ml, showing that B22 Glu plays a key role in reducing the self-association of the insulin molecule without greatly reducing its biological activity.
View Article and Find Full Text PDFEndocrinology
January 2001
Institut National de la Santé et de la Recherche Médicale U510 (F.A.), Faculté de Pharmacie Paris XI, 92296 Châtenay-Malabry, France.
The endosomal compartment of hepatic parenchymal cells contains an acidic endopeptidase, endosomal acidic insulinase (EAI), which hydrolyzes internalized insulin at a limited number of sites. Although the positions of these cleavages are partially known, the residues of insulin important in its binding to and proteolysis by EAI have not been defined. To this end, we have studied the degradation over time of native human insulin and three insulin-analog peptides using a soluble endosomal extract from rat liver parenchyma followed by purification of the products by HPLC and determination of their structure by mass spectrometry.
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