Glucose-responsive insulin represents a promising approach to regulate blood glucose levels. We previously showed that attaching two fluorophenylboronic acid (FPBA) residues to the C-terminal B chain of insulin glargine led to glucose-dependent solubility. Herein, we demonstrated that relocating FPBA from B chain to A chain increased the baseline solubility without affecting its potency. Furthermore, increasing the number of FPBA groups led to increased glucose-dependent solubility.
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http://dx.doi.org/10.3389/fchem.2022.859133 | DOI Listing |
Oncol Lett
March 2025
Department of Gastroenterology Surgery, Yichang Central People's Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei 443000, P.R. China.
Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Glycolysis serves a crucial role in the development of CRC. The aim of the present study was to investigate the function of lectin galactoside-binding soluble 4 () in the regulation of glycolysis and its therapeutic potential in CRC.
View Article and Find Full Text PDFLangmuir
July 2024
Soft Matter Physics Laboratory, School of Advanced Materials Science and Engineering, Sungkyunkwan University, Suwon 16419, South Korea.
Glucose modifies the mechanical stability of coffee films and facilitates their dissolution dynamics at the microscale, rendering glucose-coffee a valuable natural biomaterial system for studying pharmaceutical applications. We show the glucose-dependent inhibition of crack propagation during the evaporation of glucose-coffee droplets. The addition of glucose increases the hardness, stiffness, and shear modulus of films, as measured by surface nanomechanical testing.
View Article and Find Full Text PDFJ Agric Food Chem
September 2023
Institute of Biotechnology and Biochemical Engineering, Graz University of Technology, NAWI Graz, A-8010 Graz, Austria.
Sugar nucleotide-dependent glycosyltransferases are powerful catalysts of the glycosylation of natural products and xenobiotics. The low solubility of the aglycone substrate often limits the synthetic efficiency of the transformation catalyzed. Here, we explored different approaches of solvent engineering for reaction intensification of β-glycosylation of 15HCM (a C15-hydroxylated, plant detoxification metabolite of the herbicide cinmethylin) catalyzed by safflower UGT71E5 using UDP-glucose as the donor substrate.
View Article and Find Full Text PDFBioorg Med Chem
May 2023
Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States.
GPR40 AgoPAMs are highly effective antidiabetic agents that have a dual mechanism of action, stimulating both glucose-dependent insulin and GLP-1 secretion. The early lipophilic, aromatic pyrrolidine and dihydropyrazole GPR40 AgoPAMs from our laboratory were highly efficacious in lowering plasma glucose levels in rodents but possessed off-target activities and triggered rebound hyperglycemia in rats at high doses. A focus on increasing molecular complexity through saturation and chirality in combination with reducing polarity for the pyrrolidine AgoPAM chemotype resulted in the discovery of compound 46, which shows significantly reduced off-target activities as well as improved aqueous solubility, rapid absorption, and linear PK.
View Article and Find Full Text PDFNeurochem Res
July 2023
Centre for Biomolecular Interactions Bremen, Faculty 2 (Biology/Chemistry), University of Bremen, P.O. Box 330440, 28334, Bremen, Germany.
Electron cycler-mediated extracellular reduction of the water-soluble tetrazolium salt 1 (WST1) is frequently used as tool for the determination of cell viability. We have adapted this method to monitor by determining the extracellular WST1 formazan accumulation the cellular redox metabolism of cultured primary astrocytes via the NAD(P)H-dependent reduction of the electron cycler β-lapachone by cytosolic NAD(P)H:quinone oxidoreductase 1 (NQO1). Cultured astrocytes that had been exposed to β-lapachone in concentrations of up to 3 µM remained viable and showed an almost linear extracellular accumulation of WST1 formazan for the first 60 min, while higher concentrations of β-lapachone caused oxidative stress and impaired cell metabolism.
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