China
Africa
Explore chapters and articles related to this topic
Methods for Sequence Determination
Published in Roger L. Lundblad, Chemical Reagents for Protein Modification, 2020
Levy recommends the following technique for 1 to 10 nmol of peptide.16 Acid-washed polypropylene microcentrifuge tubes are used, and all manipulations of liquids are done with polypropylene micropipet tips. Argon is preferred for flushing since it is heavier than nitrogen and thus stays in the tubes better. The buffer for coupling consists of 15 ml pyridine, 1.18 ml dimethylallylamine, and 10 ml water; the pH is adjusted to 9.5 with TFA. Norleucine, 25 to 50 nmol, is added at the beginning of each cycle as a carrier and internal standard.
Melanotropic Peptides: Biomedical Applications
Published in Mac E. Hadley, The Melanotropic Peptides, 2018
Dhirendra N. Chaturvedi, Mac E. Hadley
We reported the successful synthesis of a tritium-labeled melanotropin.54 Ac-[Nle4,D-Phe7]α-MSH4-11-NH2, an octapeptide, was a superpotent agonist of frog and lizard skin melanocytes and mouse S91 (Cloudman) melanoma cells. This melanotropin possessed ultraprolonged activity on melanocytes, both in vitro and in vivo, and the peptide was resistant to inactivation by serum and purified proteolytic enzymes. The tritium-labeled congener was prepared by direct incorporation of [3H]-labeled norleucine into the peptide. The melanotropic activity of the labeled peptide, as expected, was identical to the unlabeled analog.54
Medication: Nanoparticles for Imaging and Drug Delivery
Published in Harry F. Tibbals, Medical Nanotechnology and Nanomedicine, 2017
A number of other PEGylated enzymes are undergoing clinical development, including PEG-recombinant arginine deiminase (rhArg) as a treatment for hepatocellular carcinoma both as a single agent, to deplete arginine, and also in combination with 5-fluorouracil (5-FU). A combination of PEGylated-glutaminase (PEG-glut) and the glutamine antimetabolite 6-diazo-5-oxo-l-norleucine (DON) is also being clinically evaluated, based on the hypothesis that DON will be more effective when glutamine levels are depleted.
Distinct maternal amino acids and oxylipins predict infant fat mass and fat-free mass indices
Published in Archives of Physiology and Biochemistry, 2023
Monika Riederer, Marlies Wallner, Natascha Schweighofer, Bianca Fuchs-Neuhold, Anna Rath, Andrea Berghold, Katharina Eberhard, Andrea Groselj-Strele, Wolfgang Staubmann, Marie Peterseil, Irmgard Waldner, Johannes A. Mayr, Michael Rothe, Sandra Holasek, Susanne Maunz, Elisabeth Pail, Moenie van der Kleyn
Free AA were determined in maternal serum samples of T1, T2, and T3 and in breast milk samples of T3 (see Supplemantary Table 1a for descriptive data). Breast milk samples were centrifuged at 10,000 g for 5 min and analysed after removing the fat layer. The concentration of free AA was determined from serum or breast milk via ion-exchange chromatography followed by postcolumn derivatization with ninhydrin using the Biochrom 30+ AA Analyser Physiological System (Biochrom Ltd., Cambridge, UK). Serum samples were deproteinized by mixing 100 µl serum with 100 µl Seraprep (Pickering Laboratories, Mountain View, CA) and adding 10 µl of 210 µmol/l norleucine as internal standard. After incubation for 30 min on ice, the samples were centrifuged at 10,000 g for 5 min. The supernatant was collected and filtered through a 0.2 µm centrifugal filter (Laborservice Onken, Gründau-Breitenborn, Germany). The flow-through was collected and 30 µl were loaded on the AA analyser. For quantification, an AA standard mixture (Laborservice Onken, Gründau-Breitenborn, Germany) was analysed after at least every 20th sample. For quality control, the analysing laboratory takes part in the ERNDIM EQA scheme for AA (https://www.erndim.org).
New insights into the metabolism of Th17 cells
Published in Immunological Medicine, 2023
Senescent T cells also focus on the pathogenesis of autoimmune diseases. They produce various inflammatory cytokines and chemokines. Similar to CD8 T cells, CD4 T cells may undergo cellular senescence during chronic inflammation and arrest the surface expression of CD28 [100]. CD4+CD28- T cells from patients with rheumatoid arthritis show a preferential polarization toward the Th17 phenotype that expresses RORγt [101]. Several studies have shown that senescent CD4+CD28- T cells produce more IL-17, IFNγ and RANKL than CD4+CD28+ T cells [102–105]. Notably, Foxp3+CD4+CD28- T cells downregulate CD25 and decrease suppressive capacity, while increasing the expression levels of TNFα and IL-17A [105]. Upon activation, CD4 T cells from old mice have impaired OXPHOS and glycolysis, and they depend primarily on glutaminolysis. Inhibition of glutaminolysis by 6-diazo-5-oxo-l-norleucine (DON) significantly reduced IFNγ production in CD4 T cells from old mice, but not from young mice [106]. Moreover, it has been reported that not only CD4 T cells from old mice, but also senescent cells are sensitive to Gls1 inhibition [107]. Inhibition of Gls1 specifically eliminates senescent cells and ameliorates age-associated organ dysfunction [107].
Transglutaminase 2 as a therapeutic target for neurological conditions
Published in Expert Opinion on Therapeutic Targets, 2021
Jeffrey W. Keillor, Gail V.W. Johnson
More extensive peptide sequences have also been used as high-affinity scaffolds for TG2 inhibitors bearing electrophilic warheads on their side chains. For example, in 2003 the Khosla group published a series of peptides incorporating either acivicin (an analog of glutamine) or DON (6-diazo-5-oxo-norleucine) in a sequence derived from a gluten peptide [48]. An inhibitor of this type (DMP1, Figure 4C) was later used to inhibit TG2, prior to its crystallization in its open conformation (PDB 2Q3Z, see Figure 3A) [29]. The same approach was adopted by N Zyme Biotech, who were issued a patent in 2005 for the use of Cbz-DON-Gly as a transglutaminase inhibitor [36]. Since 2006, an inhibitor based on the more extended sequence of Cbz-DON-Val-Pro-Leu-OMe has been sold by Zedira under the name of Z-DON (Figure 4C), an inhibitor used extensively as a research tool. The structure of TG2 inhibited with Z-DON (PDB 3S3J) was deposited in 2011 and shows high similarity to the structure of 2Q3Z shown in Figure 3A. It should also be mentioned that a peptidomimetic irreversible inhibitor developed by Zedira, named ZED1227 (Figure 4C), is the first small molecule TG2-selective inhibitor to enter clinical trials, and has recently successfully completed Phase 2a trials for the treatment of celiac disease [49].