122210-05-3Relevant articles and documents
O-GlcNAcylation of truncated NAC segment alters peptide-dependent effects on α-synuclein aggregation
Davey, Andrew K.,Kassiou, Michael,Mellick, George D.,Rudrawar, Santosh,Ryan, Philip,Xu, Ming-ming
, (2019)
Numerous post-translational modifications (PTMs) of the Parkinson's disease (PD) associated α-synuclein (α-syn) protein have been recognised to play critical roles in disease aetiology. Indeed, dysregulated phosphorylation and proteolysis are thought to modulate α-syn aggregation and disease progression. Among the PTMs, enzymatic glycosylation with N-acetylglucosamine (GlcNAc) onto the protein's hydroxylated amino acid residues is reported to deliver protective effects against its pathogenic processing. This modification has been reported to alter its pathogenic self-assembly. As such, manipulation of the protein's O-GlcNAcylation status has been proposed to offer a PD therapeutic route. However, targeting upstream cellular processes can lead to mechanism-based toxicity as the enzymes governing O-GlcNAc cycling modify thousands of acceptor substrates. Small glycopeptides that couple the protective effects of O-GlcNAc with the selectivity of recognition sequences may prove useful tools to modulate protein aggregation. Here we discuss efforts to probe the effects of various O-GlcNAc modified peptides on wild-type α-synuclein aggregation.
Regioselective phenol or carbinol glycosidation of 17β-estradiol and derivatives thereof
Adinolfi, Matteo,Iadonisi, Alfonso,Pezzella, Alessandro,Ravidà, Alessandra
, p. 1848 - 1852 (2005)
Unprecedented regioselective glycosidations of 17β-estradiol and nitro substituted derivatives thereof either at the phenol or carbinol position is reported. In the former case, glycosyl bromides or iodides were employed as the donors in a base promoted reaction conducted under two-phase conditions. In the latter case, glycosyl trichloroacetimidate donors were used in combination with the mild activation of 4 A? acid washed molecular sieves. Georg Thieme Verlag Stuttgart.
A facile and efficient method for synthesis of macrocyclic lipoglycopeptide
Zhao, Qingjie,Li, Xiang,Li, Wenjuan,Zou, Yan,Hu, Honggang,Wu, Qiuye
, p. 1018 - 1022 (2015)
An efficient and practical method for macrocyclic lipoglycopeptide synthesis was developed and utilized to synthesize lipoglycosylated derivatives of Tyrocidine A. The method is based on solid-phase peptide synthesis using 2-chlorotrityl resin as the soli
Synthesis of ureido thioglycosides as novel insect β?N?acetylhexosaminidase OfHex1 inhibitors
Dong, Lili,Dong, Yanhong,Lu, Huizhe,Shen, Shengqiang,Yang, Qing,Zhang, Jianjun
, (2020)
The insect β-N-acetylhexosaminidase OfHex1 from Ostrinia furnacalis (one of the most destructive agricultural pests) has been considered as a promising pesticide target. In this study, a series of novel and readily available ureido thioglycosides were designed and synthesized based on the catalytic mechanism and the co-crystal structures of OfHex1 with substrates. After evaluation via enzyme inhibition experiments, thioglycosides 11c and 15k were found to have inhibitory activities against OfHex1 with the Ki values of 25.6 μM and 53.8 μM, respectively. In addition, all these ureido thioglycosides exhibited high selectivity toward OfHex1 over hOGA and HsHexB (Ki > 100 μM). Furthermore, to investigate the inhibitory mechanism, the possible binding modes of 11c and 15k with OfHex1 were deduced based on molecular docking analysis. This work may provide useful structural starting points for further rational design of potent inhibitors of OfHex1.
Synthesis and cytotoxicity of the conjugates of diterpenoid isosteviol and N-acetyl-D-glucosamine
Garifullin, Bulat F.,Strobykina, Irina Yu.,Khabibulina, Leysan R.,Sapunova, Anastasiya S.,Voloshina, Aleksandra D.,Sharipova, Radmila R.,Khairutdinov, Bulat I.,Zuev, Yuriy F.,Kataev, Vladimir E.
, p. 1372 - 1378 (2019/08/22)
A series of conjugates of diterpenoid isosteviol (16-oxo-ent-beyeran-19-oic acid) and N-acetyl-D-glucosamine was synthesised and their cytotoxicity against several human cancer cell lines (M-Hela, MCF-7, Hep G2, Panc-1, PC-3), as well as normal human cell lines (WI-38, Chang liver) was assayed. Most of the conjugates were found to be cytotoxic against the mentioned cancer cell lines in the range of IC50 values 13–89 μM. Two lead compounds 14a and 14b showed selective cytotoxicity against M-Hela (IC50 13 and 14 μM) that was two times as high as the cytotoxicity of the anti-cancer drug Tamoxifen in control (IC50 28 μM). It was found that cytotoxic activity of the lead compounds against M-Hela cells is due to induction of apoptosis.
Glycosides and Glycoconjugates of the Diterpenoid Isosteviol with a 1,2,3-Triazolyl Moiety: Synthesis and Cytotoxicity Evaluation
Andreeva, Olga V.,Garifullin, Bulat F.,Sharipova, Radmila R.,Strobykina, Irina Yu.,Sapunova, Anastasiya S.,Voloshina, Alexandra D.,Belenok, Mayya G.,Dobrynin, Alexey B.,Khabibulina, Leysan R.,Kataev, Vladimir E.
, p. 2367 - 2380 (2020/08/28)
Several glycoconjugates of the diterpenoid isosteviol (16-oxo-ent-beyeran-19-oic acid) with a 1,2,3-triazolyl moiety were synthesized, and their cytotoxicity was evaluated against some human cancer and normal cell lines. Most of the synthesized compounds demonstrated weak inhibitory activities against the M-HeLa and MCF-7 human cancer cell lines. Three lead compounds, 54, 56 and 57, exhibited high selective cytotoxic activity against M-HeLa cells (IC50 = 1.7-1.9 μM) that corresponded to the activity of the anticancer drug doxorubicin (IC50 = 3.0 μM). Moreover, the lead compounds were not cytotoxic with respect to a Chang liver human normal cell line (IC50 > 100 μM), whereas doxorubicin was cytotoxic to this cell line (IC50 = 3.0 μM). It was found that cytotoxic activity of the lead compounds is due to induction of apoptosis proceeding along the mitochondrial pathway. The present findings suggest that 1,2,3-triazolyl-ring-containing glycoconjugates of isosteviol are a promising scaffold for the design of novel anticancer agents.
