- Rapid phenolic O-glycosylation of small molecules and complex unprotected peptides in aqueous solvent
-
Glycosylated natural products and synthetic glycopeptides represent a significant and growing source of biochemical probes and therapeutic agents. However, methods that enable the aqueous glycosylation of endogenous amino acid functionality in peptides without the use of protecting groups are scarce. Here, we report a transformation that facilitates the efficient aqueous O-glycosylation of phenolic functionality in a wide range of small molecules, unprotected tyrosine, and tyrosine residues embedded within a range of complex, fully unprotected peptides. The transformation, which uses glycosyl fluoride donors and is promoted by Ca(OH)2, proceeds rapidly at room temperature in water, with good yields and selective formation of unique anomeric products depending on the stereochemistry of the glycosyl donor. High functional group tolerance is observed, and the phenol glycosylation occurs selectively in the presence of virtually all side chains of the proteinogenic amino acids with the singular exception of Cys. This method offers a highly selective, efficient, and operationally simple approach for the protecting-group-free synthesis of O-aryl glycosides and Tyr-O-glycosylated peptides in water.
- Wadzinski, Tyler J.,Steinauer, Angela,Hie, Liana,Pelletier, Guillaume,Schepartz, Alanna,Miller, Scott J.
-
p. 644 - 652
(2018/05/04)
-
- Toxicity and metabolism of p-chlorophenol in the marine microalga Tetraselmis marina
-
Toxicity and metabolism of para-chlorophenol (p-CP) in the marine microalga Tetraselmis marina have been studied. The inhibition constant EC50 for p-CP was 272 ± 17 μM (34.8 ± 2.2 mg L-1) under the experimental conditions. Two metabolites were detected in the growth medium in the presence of p-CP by reverse phase HPLC and their concentrations increased at the expense of p-CP. The two metabolites, which were found to be more polar than p-CP, were isolated by a C18 column. They were identified as p-chlorophenyl-β-d-glucopyranoside (p-CPG) and p-chlorophenyl-β-d-(6-O-malonyl)-glucopyranoside (p-CPGM) by electrospray ionization-mass spectrometric analysis in a negative ion mode. The molecular structures of p-CPG and p-CPGM were further confirmed by enzymatic and alkaline hydrolyses. Treatment with β-glucosidase released free p-CP and glucose from p-CPG, whereas p-CPGM was completely resistant. Alkaline hydrolysis completely cleaved the esteric bond of the malonylated glucoconjugate and yielded p-CPG and malonic acid. It was concluded that the pathway of p-CP metabolism in T. marina involves an initial conjugation of p-CP to glucose to form p-chlorophenyl-β-d-glucopyranoside, followed by acylation of the glucoconjugate to form p-chlorophenyl-β-d-(6-O-malonyl)-glucopyranoside. The metabolism of p-CP in T. marina was mainly driven by photosynthesis, and to a lesser extent by anabolic metabolism in the dark. Accordingly, the detoxification rate under light was about seven times higher than in the darkness. This work provides the first evidence that microalgae can adopt a combined glucosyl transfer and malonyl transfer process as a survival strategy for detoxification of such xenobiotics as p-CP.
- Petroutsos, Dimitris,Wang, Jiangxin,Katapodis, Petros,Kekos, Dimitris,Sommerfeld, Milton,Hu, Qiang
-
p. 192 - 201
(2008/02/13)
-
