116783-35-8Relevant articles and documents
Piperidine is preferred to morpholine for Fmoc cleavage in solid phase glycopeptide synthesis as exemplified by preparation of glycopeptides related to HIV gp120 and mucins
Vuljanic, Tatjana,Bergquist, Karl-Erik,Clausen, Henrik,Roy, Sarbani,Kihlberg, Jan
, p. 7983 - 8000 (1996)
Protected derivatives of the Tn antigens [Fmoc-Ser/Thr(Ac3GalNAcα)-OH, compounds 5 and 8] have been prepared by glycosylation of Fmoc-Ser/Thr- OAllyl with 3,4,6-tri-O-acetyl-2-azido-2-deoxy-D-galactopyranosyl chloride (2), followed by conversion of the azido group to an acetamide and deallylation. The derivatives 5 and 8 were used for solid phase synthesis of glycopeptides related to HIV gp120 and mucins. In these syntheses piperidine was found to give efficient Fmoc removal whereas deprotection with morpholine was slow and incomplete for some steps. In contrast to previous concerns β- elimination and epimerization of glycopeptide stereocenters was not encountered when piperidine was used for Fmoc deprotection. However, it was found that for glycopeptides which contained cysteine residues, de-O- acetylation with methanolic ammonia had to be performed before side-chain deprotection and cleavage from the solid phase.
Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)
Urbańczyk, Ma?gorzata,Jewgiński, Micha?,Krzciuk-Gula, Joanna,Góra, Jerzy,Latajka, Rafa?,Sewald, Norbert
, p. 1581 - 1591 (2019)
Antifreeze glycoproteins are a class of biological agents which enable living at temperatures below the freezing point of the body fluids. Antifreeze glycopeptides usually consist of repeating tripeptide unit (-Ala-Ala-Thr?-), glycosylated at the threonine side chain. However, on the microscopic level, the mechanism of action of these compounds remains unclear. As previous research has shown, antifreeze activity of antifreeze glycopeptides strongly relies on the overall conformation of the molecule as well an on the stereochemistry of amino acid residues. The desired monoglycosylated analogues with acetylated amino termini and the carboxy termini in form of N-methylamide have been synthesized. Conformational nuclear magnetic resonance (NMR) studies of the designed analogues have shown a strong influence of the stereochemistry of amino acid residues on the peptide chain stability, which could be connected to the antifreeze activity of these compounds. A better understanding of the mechanism of action of antifreeze glycopeptides would allow applying these materials, e.g., in food industry and biomedicine.
Methyl esters: an alternative protecting group for the synthesis of O-glycosyl amino acid building blocks
Mayato, Carlos,Dorta, Rosa L.,Vázquez, Jesús T.
, p. 1396 - 1398 (2008)
The glycosyl amino acids α-GalNAc-Ser and α-GalNAc-Thr are fundamental building blocks for glycopeptide synthesis, Schmidt's synthesis method often being chosen for this purpose. Methyl esters used as orthogonal carboxylic acid protecting group in this pr
Fluorenylmethoxycarbonyl-Protected O-Glycosyl-N-methyl Amino Acids: Building Blocks for the Synthesis of Conformationally Tuned Glycopeptide Antigens
Buba, Annette E.,L?we, Holger,Kunz, Horst
, p. 5764 - 5774 (2015)
Peptide antibiotics often contain N-methylated amino acids. These N-methylamino components enhance the metabolic stability and strongly influence the conformational behavior of these peptide drugs. N-Methyl-O-glycosyl amino acids, in particular, threonine and serine derivatives, are unknown so far. Fmoc-protected N-methyl-O-glycosyl-threonine and -serine building blocks, including sialyl TN antigens, have been synthesized for the first time by converting the Fmoc-protected O-glycosyl amino acids or their tert-butyl esters into the corresponding oxazolidinones followed by reductive ring-opening. These new components are considered interesting for the construction of modified mucin glycopeptide anti-tumor vaccines with extended biological half-life. Fmoc-protected building blocks of N-methylated O-glycosyl amino acids, inaccessible so far, have been synthesized by the conversion of Fmoc-O-glycosyl amino acids into the corresponding oxazolidines followed by reductive ring-opening. These N-methyl-O-glycosyl amino acids could be used in solid-phase glycopeptide syntheses under particular conditions.
Design and synthesis of trivalent Tn glycoconjugate polymers by nitroxide-mediated polymerization
Liu, Si-Xian,Tsai, Yun-Tzu,Lin, Yu-Tung,Li, Jia-Yue,Chang, Che-Chien
, (2019/11/26)
A new synthetic method for preparing Tn glycoconjugate polymers, containing tumor-associated carbohydrate antigens, by controlled living radical polymerization is reported. To mimic the authentic structures of Tn glycopeptide antigens and to explore the controlled living radical polymerization, three tumor-associated carbohydrate antigens (GalNAc, GalNAcα1-O-Ser, and GalNAcα1-O-Thr) were attached to a styrene-type monomer through a diethylene glycol spacer. Under nitroxide-mediated polymerization, controlled living radical polymerization proceeded to afford defined glycopeptide polymers with different Tn densities and compositions. The polydispersity index (PDI) and molecular weights were increased and conversions were decreased upon increasing the concentration of Tn glycoconjugate monomers. The resulting Tn glycoconjugate polymers were characterized by NMR and IR. The spectral data indicate that the Tn glycoconjugate moiety did attach to the polymer chain and Tn glycoconjugate density could be adjusted through the nitroxide-mediated polymerization conditions. The number of Tn units containing in the polymer chains could be estimated by NMR integration. This synthetic approach provides a new and efficient tool for constructing novel Tn glycoconjugate polymers.
Synthetic MUC1 antitumor vaccine with incorporated 2,3-sialyl-T carbohydrate antigen inducing strong immune responses with isotype specificity
Stra?burger, David,Glaffig, Markus,Stergiou, Natascha,Bialas, Sabrina,Besenius, Pol,Schmitt, Edgar,Kunz, Horst
, p. 1142 - 1146 (2018/10/21)
The endothelial glycoprotein MUC1 is known to underlie alterations in cancer by means of aberrant glycosylation accompanied by changes in morphology. The heavily shortened glycans induce a collapse of the peptide backbone and enable accessibility of the latter to immune cells, rendering it a tumor-associated antigen. Synthetic vaccines based on MUC1 tandem repeat motifs, comprising tumor-associated 2,3-sialyl-T antigen, conjugated to the immunostimulating tetanus toxoid, are reported herein. Immunization with these vaccines in a simple water/oil emulsion produced a strong immune response in mice to which stimulation with complete Freund’s adjuvant (CFA) was not superior. In both cases, high levels of IgG1 and IgG2a/b were induced in C57BL/6 mice. Additional glycosylation in the immunodominant PDTRP domain led to improved binding of the induced antisera to MCF-7 breast tumor cells, compared with that of the monoglycosylated peptide vaccine.
