Clinical Considerations in Radiotracer Biodistribution Studies
Lelio G. Colombetti in Biological Transport of Radiotracers, 2020
Lipid bilayer membranes are highly impermeable to small inorganic ions. A variety of molecules, including the antibiotics valinomycin and nonactin, interact with lipid bilayer membranes and increase their permeability to small ions via a carrier mechanism comparable to the highly ion-permeable nerve membranes. Other membrane-modifying molecules, such as gramicidin A and alamethicin, facilitate the passive diffusion of ions by creating a pathway through the membrane through which ions can move down an electrochemical gradient. Other pore-forming antibiotics are nystatin and amphotericin B.10
Biomedical Applications of Raman Scattering
R. Michael Gendreau in Spectroscopy in the Biomedical Sciences, 1986
A variety of Raman spectroscopic studies have appeared along these general lines. The interaction of lysozyme (not an integral membrane protein) with liposomes formed from a mixture of the phospholipids 1,2-dipalmitoyl-L-phosphatidic acid/1,2 dimyristoyl-L-phosphatidylcholine was studied by Lippert et al.81 At temperatures < 27°C, interaction of protein with lipid slightly increased the amount of helical structure in lysozyme, while above 30°C, considerable β-sheet was formed. The onset of β-structure was accompanied by the introduction of disorder into the lipid side chains. The results were interpreted in terms of both polar interactions between the acidic lipid component at temperatures where the lipids are in the gel state and hydrophobic interactions between lipid and protein at higher temperatures. Lis et al.82 examined the effect of the ionophores alamethicin and valinomycin on phospholipid organization. Both peptides tended to fluidize dimyristoyl lecithin but produced little alteration in the chain conformation of dipalmitoyl lecithin (DPPC). Detailed temperature studies were not reported. In contrast, Verma and Wallach83 suggested that the peptide mellitin tends to rigidify DPPC multibilayers. In a more thorough investigation of the same system,84 Levin and co-workers demonstrated two melting events when the peptide was inserted into dimyristoylphosphatidylcholine (DMPC). The primary gel/liquid-crystal transition is depressed when the peptide concentration is increased. The concentration-independent higher-temperature transition is associated with the melting of lipids present at the lipid-polypeptide interface. It was estimated that about six lipid molecules fall into this category.
Mass Spectrometric Analysis
Adorjan Aszalos in Modern Analysis of Antibiotics, 2020
Alamethicin I (Figure 2) has also been characterized by californium-252 PD [247]. The positive ion spectrum is more helpful, providing (M + Na)+ and (M + 2Na − H)+ adduct ions and fragment ions, which coincides with the peptide sequence; N-imine ions corresponding to cleavages of 16 of the 19 peptide bonds are observed. The negative ion spectrum exhibits a (M − H)− ion but few useful fragment ions.
Characterisation of UDP-glucuronosyltransferase activity in sea turtle Chelonia mydas
Published in Xenobiotica, 2022
Vera Helena V. Dias, Jacó J. Mattos, Camila L. V. Bastolla, Karim H. Lüchmann, Afonso C. D. Bainy
Lithocholic acid, taurocholic acid, diclofenac, ibuprofen, and paracetamol were screened as inhibitors of UGT enzymes. Activity assays were performed in liver microsomes (as described earlier) in the presence of chemical inhibitors (100 µM final concentration). Besides substrates and inhibitors, we only used alamethicin (22 µg/mg of protein) as a membrane-disrupting agent. Methanol concentration was below 0.5%.4-MU final concentration (100 µM) was lower than in other assays, since high substrate concentration reduces this inhibition. Nevertheless, the concentration of 100 µM of 4-MU used in the inhibitors experiment may underestimate the potential effects of some weak inhibitors, mainly the competitive type. Thus, the results should be interpreted with caution, as some potential inhibitors tested here may show an inhibitory effect on enzyme activity at lower 4-MU concentrations, which were not examined in this study.
In vitro modulatory effects of ginsenoside compound K, 20(S)-protopanaxadiol and 20(S)-protopanaxatriol on uridine 5′-diphospho-glucuronosyltransferase activity and expression
Published in Xenobiotica, 2021
Su-Nyeong Jang, So-Young Park, Hyunyoung Lee, Hyojin Jeong, Ji-Hyeon Jeon, Im-Sook Song, Mi Jeong Kwon, Kwang-Hyeon Liu
Androsterone, berberine, chenodeoxycholic acid (CDCA), cotinine, carvedilol, estrone-β-D-glucuronide (EG), schisandrin A, N-acetylserotonin, naloxone, testosterone, trifluoperazine, and uridine 5′-diphospho-glucuronic acid (UDPGA) were purchased from Sigma-Aldrich (St. Louis, MO). 7-ethyl-10-hydroxy camptothecin (SN-38) was provided by Santa Cruz Biotechnology (Dallas, TX). Alamethicin (from Trichoderma viride), CDCA 24-acyl-β-D-glucuronide, and mycophenolic acid were obtained from Toronto Research Chemicals (Toronto, ON, Canada). CK (98.0%), PPD (98.0%), and PPT (98.0%) were purchased from the Ambo Institute (Daejeon, Korea). All solvents were liquid chromatography-tandem mass spectrometry (LC-MS/MS) grade (Fisher Scientific, Pittsburgh, PA). Pooled human liver microsomes (HLMs, H2630, and mixed gender) were obtained from XenoTech (Lenexa, KS, USA)), and rUGTs (UGT1A1, 1A3, 1A4, 1A6, 1A9, 2B4, 2B7, 2B10, 2B15, and 2B17) and cryopreserved human hepatocytes (HFC520) were purchased from Corning Life Sciences (Woburn, MA, USA).
Understanding metabolism related differences in ocular efficacy of MGV354
Published in Xenobiotica, 2021
Jennifer L. Dumouchel, Upendra A. Argikar, Christopher M. Adams, Ganesh Prasanna, Takeru Ehara, Sean Kim, Chris Breen, Muneto Mogi
MGV354 was prepared as previously described (Ehara et al., 2018). Cryopreserved suspension hepatocytes (New Zealand White rabbit, male, pooled, n = 3; cynomologous monkey, male, pooled, n = 3; and human, mixed gender, pooled, n = 5) were obtained from Bioreclamation IVT (Baltimore, MD) or BioIVT (Westbury, NY). Incubation media such as InVitroGRO HT Medium supplemented with torpedo antibiotic mix and Williams E Medium were also obtained from Bioreclamation IVT. Ocular S9 fractions from New Zealand White rabbit (5 mg/mL protein, male, pooled, n = 75), cynomologous monkey (5 mg/mL protein, male, pooled, n = 6) and human (5 mg/mL protein, mixed gender, pooled, n = 11) were custom-ordered from XenoTech LLC (Lenexa, KS). Sample extracts from plasma of monkeys were the same as generated and quantitatively evaluated for pharmacokinetics in the previously published study on animals with 1% MGV354 topical instillations, as detailed by Prasanna et al. (2018). Alamethicin from Trichoderma viride and NADPH were purchased from MP Biomedicals (Solon, OH) or Sigma Aldrich (St. Louis, MO). Solvents were LC-MS grade or higher and were procured through Mallinckrodt Baker (Phillipsburg, NJ) or Avantor (Bridgewater, NJ). All other reagents were purchased from Sigma Aldrich (St. Louis, MO).
Related Knowledge Centers
- Alpha Helix
- Antibiotic
- Molecule
- Peptide
- Cell Membrane
- Peptaibol
- Proteinogenic Amino Acid
- Protein Structure
- 2-Aminoisobutyric Acid
- Ion