scholarly journals Recent Development in the Design of Neoglycoliposomes Bearing Arborescent Architectures

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4281
Author(s):  
Leila Mousavifar ◽  
Shuay Abdullayev ◽  
René Roy

This brief review highlights systematic progress in the design of synthetic glycolipid (neoglycolipids) analogs evolving from the conventional architectures of natural glycosphingolipids and gangliosides. Given that naturally occurring glycolipids are composed of only one hydrophilic sugar head-group and two hydrophobic lipid tails embedded in the lipid bilayers of the cell membranes, they usually require extraneous lipids (phosphatidylcholine, cholesterol) to confer their stability. In order to obviate the necessity for these additional stabilizing ingredients, recent investigations have merged dendrimer chemistry with that of neoglycolipid syntheses. This singular approach has provided novel glycoarchitectures allowing reconsidering the necessity for the traditional one to two hydrophilic/hydrophobic ratio. An emphasis has been provided in the recent design of modular arborescent neoglycolipid syntheses coined glycodendrimersomes.

2016 ◽  
Vol 311 (4) ◽  
pp. G713-G723 ◽  
Author(s):  
Beng San Yeoh ◽  
Piu Saha ◽  
Vishal Singh ◽  
Xia Xiao ◽  
Yun Ying ◽  
...  

Stearoyl-CoA desaturase-1 (SCD1) is a lipogenic enzyme involved in the de novo biosynthesis of oleate (C18:1, n9), a major fatty acid in the phospholipids of lipid bilayers of cell membranes. Accordingly, Scd1KO mice display substantially reduced oleate in cell membranes. An altered SCD1 level was observed during intestinal inflammation; however, its role in modulating inflammatory bowel disease remains elusive. Herein, we investigated the colitogenic capacity of Scd1KO effector T cells by employing the adoptive T-cell transfer colitis model. Splenic effector T cells (CD4+CD25−) from age- and sex-matched wild-type (WT) and Scd1KO mice were isolated by FACS and intraperitoneally administered to Rag1KO mice, which were monitored for the development of colitis. At day 60 postcell transfer, Rag1KO mice that received Scd1KO CD4+CD25− T cells displayed accelerated and exacerbated colitis than mice receiving WT CD4+CD25− T cells. Intriguingly, Scd1KO CD4+CD25− T cells display augmented inflammatory cytokine profile and cellular membrane fluidity with a concomitant increase in proinflammatory saturated fatty acids, which we postulate to potentially underlie their augmented colitogenic potential.


2008 ◽  
Vol 105 (40) ◽  
pp. 15287-15292 ◽  
Author(s):  
Rodney E. Infante ◽  
Michael L. Wang ◽  
Arun Radhakrishnan ◽  
Hyock Joo Kwon ◽  
Michael S. Brown ◽  
...  

Egress of lipoprotein-derived cholesterol from lysosomes requires two lysosomal proteins, polytopic membrane-bound Niemann–Pick C1 (NPC1) and soluble Niemann–Pick C2 (NPC2). The reason for this dual requirement is unknown. Previously, we showed that the soluble luminal N-terminal domain (NTD) of NPC1 (amino acids 25–264) binds cholesterol. This NTD is designated NPC1(NTD). We and others showed that soluble NPC2 also binds cholesterol. Here, we establish an in vitro assay to measure transfer of [3H]cholesterol between these two proteins and phosphatidylcholine liposomes. Whereas NPC2 rapidly donates or accepts cholesterol from liposomes, NPC1(NTD) acts much more slowly. Bidirectional transfer of cholesterol between NPC1(NTD) and liposomes is accelerated >100-fold by NPC2. A naturally occurring human mutant of NPC2 (Pro120Ser) fails to bind cholesterol and fails to stimulate cholesterol transfer from NPC1(NTD) to liposomes. NPC2 may be essential to deliver or remove cholesterol from NPC1, an interaction that links both proteins to the cholesterol egress process from lysosomes. These findings may explain how mutations in either protein can produce a similar clinical phenotype.


2014 ◽  
Vol 106 (2) ◽  
pp. 188a-189a ◽  
Author(s):  
Hongyu Li ◽  
Germinal Magro ◽  
Luke W. Judd ◽  
Peter R. Brotherhood ◽  
David N. Sheppard ◽  
...  

2013 ◽  
Vol 57 (10) ◽  
pp. 4963-4970 ◽  
Author(s):  
Liang Xu ◽  
Lifeng Cai ◽  
Xueliang Chen ◽  
Xifeng Jiang ◽  
Huihui Chong ◽  
...  

ABSTRACTDiscovery of new drugs for the treatment of AIDS typically possessing unique structures associated with novel mechanisms of action has been of great importance due to the quick drug-resistant mutations of HIV-1 strains. The work presented in this report describes a novel class of DNA duplex-based HIV-1 fusion inhibitors. Hydrophobic groups were introduced into a DNA duplex skeleton either at one end, at both ends, or in the middle. These modified DNA duplexes inhibited fusion between HIV-1 and human cell membranes at micro- or submicromolar concentrations. Respective inhibitors adopted an aptamer pattern instead of a base-pairing interaction pattern. Structure-activity relationship studies of the respective DNA duplexes showed that the rigid and negatively charged DNA skeletons, in addition to the presence of hydrophobic groups, were crucial to the anti-HIV-1 activity of these compounds. A fluorescent resonance energy transfer (FRET)-based inhibitory assay showed that these duplex inhibitors interacted with the primary pocket in the gp41 N-terminal heptad repeat (NHR) instead of interacting with the lipid bilayers.


2017 ◽  
Vol 43 (13-16) ◽  
pp. 1247-1255 ◽  
Author(s):  
Yoshimichi Andoh ◽  
Siti Nor Syafawani Mohamed ◽  
Sakiho Kitou ◽  
Susumu Okazaki

Biochemistry ◽  
1985 ◽  
Vol 24 (3) ◽  
pp. 573-581 ◽  
Author(s):  
Ranajit Pal ◽  
William A. Petri ◽  
Vered Ben-Yashar ◽  
Robert R. Wagner ◽  
Yechezkel Barenholz

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