The Chemical Synthesis of Lipid A
Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison in Endotoxin in Health and Disease, 2020
The anomeric a-configuration is retained in both of them. A malonic acid-type structure [-CH(C02H)2] where two carboxyl groups are located on the same carbon atom is not stable and readily loses one of them as carbon dioxide; the -CH(CH2C02H)2 structure in 23 is the minimum one containing two equivalent carboxyl groups. The distance between acidic moieties and the glucosamine residues are not the same in 23 and 24. Furthermore, fatty acyl groups in these compounds are also different from the natural ones. Therefore, no direct effects of the substitution of the phosphate into carboxylic acid can be discussed. Nevertheless, it was again confirmed that the glycosyl phosphate can be replaced with other acidic group without loss of activity. It should be noted here that oxidation of the aldehyde function in 21 into a carboxyl group gives easy and direct access to carboxymethyl analogs like 24.
Regulation of Mammalian Hexokinase Activity
Rivka Beitner in Regulation of Carbohydrate Metabolism, 1985
Sols and Crane154 had reported that there was no detectable difference in the rate with which the α- and β-anomers of glucose were phosphorylated by brain (type I) hexokinase. However, more recent studies by Okuda et al.157 have indicated that the type I enzyme from several rat tissues exhibited Vmax values with the p-anomer that were approximately 1.5 times larger than those with the α-anomer. A similar ratio in Vmax values was seen with the type II and III isozymes. Since no standard deviations were indicated, it is not possible to assess whether the slight differences between the Vmax ratios (β/α) for the different isozymes, or between the same isozyme from different tissues, were significant. In any case, based on these results, it would appear that all three isozymes are similar in preferring the β-anomer, with Vmax ratios (β/α) of about 1.5.157 These results, coupled with an overall similarity in substrate specificity (Section III.D.3) suggest a corresponding structural similarity in the hexose binding sites of the three isozymes.
Role of Tumor Cell Membrane in Hyperthermia
Leopold J. Anghileri, Jacques Robert in Hyperthermia In Cancer Treatment, 2019
Glycoproteins and glycolipids are components in the plasma membrane of all mammalian cells. Glycoproteins usually contain multiple sugar chains with different structures. The identification of the carbohydrate moieties of a great number of glycoproteins and glycolipids has been accomplished during the last two decades.97,98 All sugar molecules in a glycoprotein are attached to the polypeptide backbone as side chains of oligosaccharides or polysaccharides that are formed by O-glycosidic bonds between carbon-1 (the anomeric carbon) of one monosaccharide and any of three or more ring carbons of another monosaccharide. Alpha- or beta-glycosidic linkages can be formed by the anomeric carbon; in each case the oxygen atom is below or above the plane of the sugar ring, respectively. The carbohydrate-peptide linkage takes place through the terminal reducing groups of these oligo- or polysaccharides (Figure 6). Pronase digestion of glycoproteins and analysis of the isolated glycopeptides has been the method used to isolate carbohydrate chains for structural analysis.99
Synthesis, antiasthmatic, and insecticidal/antifungal activities of allosamidins
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
Gangliang Huang, Hualiang Huang
The synthesis of disaccharide and trisaccharide thiazolines 24 and 25 began with octaacetylchitobiose 26 and undecaacetylchitotriose 27 in turn (Scheme 6)56. The α-configuration of acetoxy groups of compounds 26 and 27 was reversed to give the corresponding β-anomers, the anomeric chlorides were obtained by the initial treatment with HCl and AcOH, and then treated with AgOAc/AcOH. After treatment with Lawesson reagent, thiazolines 28 and 29 were obtained by affecting both the conversion of amides to thioamides and the intramolecular substitution of adjacent thioamide sulfur atom to the anomeric β-acetoxy group. The partial deacetylation of per-O-acetylated thiazolines 28 and 29 gave two additional chitinase inhibitors, namely the chitobiose thiazoline thioamide 30 in a yield of 89% and chitotriose thiazoline dithioamide 31 in a yield of 80%. To synthesize target compounds 24 and 25, thioamides 28 and 29 were converted to diacetylimides 32 and 33 (81% and 60% yields in turn) with silver acetate/dichloromethane without destroying the thiazoline part. Finally, chitobiose thiazoline 24 (69% yield) and chitotriose thiazoline 25 (78% yield) were obtained by O-deacylation and mono-N-deacylation of imides 32 and 33 with sodium methanol/methanol.
Pharmacokinetics, metabolism and off-target effects in the rat of 8-[(1H- benzotriazol-1-yl)amino]octanoic acid, a selective inhibitor of human cytochrome P450 4Z1: β-oxidation as a potential augmenting pathway for inhibition
Published in Xenobiotica, 2021
John P. Kowalski, Robert D. Pelletier, Matthew G. McDonald, Edward J. Kelly, Allan E. Rettie
Analysis of pooled plasma in ESI- mode revealed many of the same metabolites as seen in ESI+ and again, M3 and M9 were majorly represented. As expected, the metabolite profile was increased and totalled 25 between the two modes of ionization, with glucuronide conjugates being newly revealed. M20 at 7.8 min, and M22, denoting the cluster of peaks from 8.3 to 8.6 min, showed fragmentation indicative of acyl-glucuronides. These likely represent a mixture of the 1-β anomer as well as the 2-, 3- and 4-α/β acyl-glucuronide anomers akin to that seen in mouse metabolism of diclofenac (Sarda et al.2012). Furthermore, M21 and M23 were identified as ions with fragmentation indicating that they were acyl-glucuronide structures that had lost their ABT moiety. These metabolites had overlapping retention times with the presumed acyl-glucuronide cluster and therefore may be artifactually generated via in-source fragmentation of M22 or sample work-up. Regardless, acyl-glucuronidation was identified as an additional biotransformation pathway for 8-BOA.
Investigation of TF-binding lectins from dietary sources and SRL on proliferation and cell cycle progression in human colon HT29 and SW620 cells
Published in Nutrition and Cancer, 2019
Shivakumar Belur, Srikanth Barkeer, Bale M. Swamy, Lu-Gang Yu, Shashikala R. Inamdar
Although all these lectins recognize TF antigen, these lectins are different in their sugar binding specificity toward addition on TF by other sugar residues. PNA binding to TF requires free hydroxyl groups at C-3 and C-6 of Gal but not at C-6 of GalNAc (24), whereas ACA binding requires free hydroxyl groups at C-4 of Gal and C-4 of GalNAc (25). ABL binding to TF requires a free hydroxyl group at C-6 of GalNAc, but is not affected by substitution at C-3 or C-6 of Gal (24), whilst JAC also requires free hydroxyl group at C-6 of GalNAc, similar to ABL, but unlike ABL, also requires free hydroxyl group at C-4 of GalNAc (26). SRL binding to TF requires a free axial hydroxyl groups at C4 of GalNAc similar to JAC and also C2 of Gal unlike other TF binding lectins (27). Apart from these binding differences, these TF binding lectins also have distinct binding affinity towards TF anomers. SRL, ACA, and JAC recognize only the “α anomer” of TFD (Galβ1- 3GalNAcα-Sp8; TFβα) whereas PNA and ABL recognizes only the “β anomer” (Galβ1-3GalNAcβ–Sp8; TFββ). Hence SRL resembles JAC and ACA more closely than PNA and ABL in binding to TF antigen (27).
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