scholarly journals Involvement of sialic acid in the regulation of  -aminobutyric acid uptake activity of  -aminobutyric acid transporter 1

Glycobiology ◽  
2010 ◽  
Vol 21 (3) ◽  
pp. 329-339 ◽  
Author(s):  
J. Hu ◽  
J. Fei ◽  
W. Reutter ◽  
H. Fan
Keyword(s):  
Sialic Acid ◽  
Aminobutyric Acid ◽  
Acid Uptake ◽  
Uptake Activity ◽  
Acid Transporter

scholarly journals Identification of a Novel Sialic Acid Transporter in Haemophilus ducreyi

2005 ◽  
Vol 73 (10) ◽  
pp. 6727-6735 ◽  
Author(s):  
Deborah M. B. Post ◽  
Rachna Mungur ◽  
Bradford W. Gibson ◽  
Robert S. Munson
Keyword(s):  
Sialic Acid ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Sialic Acid Residue ◽  
Haemophilus Ducreyi ◽  
Acid Uptake ◽  
Terminal Galactose ◽  
Genes Encoding ◽  
Acid Transporter

ABSTRACT Haemophilus ducreyi, the causative agent of chancroid, produces a lipooligosaccharide (LOS) which terminates in N-acetyllactosamine. This glycoform can be further extended by the addition of a single sialic acid residue to the terminal galactose moiety. H. ducreyi does not synthesize sialic acid, which must be acquired from the host during infection or from the culture medium when the bacteria are grown in vitro. However, H. ducreyi does not have genes that are highly homologous to the genes encoding known bacterial sialic acid transporters. In this study, we identified the sialic acid transporter by screening strains in a library of random transposon mutants for those mutants that were unable to add sialic acid to N-acetyllactosamine-containing LOS. Mutants that reacted with the monoclonal antibody 3F11, which recognizes the terminal lactosamine structure, and lacked reactivity with the lectin Maackia amurensis agglutinin, which recognizes α2,3-linked sialic acid, were further characterized to demonstrate that they produced a N-acetyllactosamine-containing LOS by silver-stained sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometric analyses. The genes interrupted in these mutants were mapped to a four-gene cluster with similarity to genes encoding bacterial ABC transporters. Uptake assays using radiolabeled sialic acid confirmed that the mutants were unable to transport sialic acid. This study is the first report of bacteria using an ABC transporter for sialic acid uptake.

scholarly journals Identification and Characterization of Inhibitors of a Neutral Amino Acid Transporter, SLC6A19, Using Two Functional Cell-Based Assays

2018 ◽  
Vol 24 (2) ◽  
pp. 111-120 ◽  
Author(s):  
Sanjay J. Danthi ◽  
Beirong Liang ◽  
Oanh Smicker ◽  
Benjamin Coupland ◽  
Jill Gregory ◽  
...  
Keyword(s):  
Amino Acid ◽  
High Throughput Screening ◽  
Amino Acid Transporter ◽  
Neutral Amino Acid ◽  
Imaging Plate ◽  
Acid Uptake ◽  
Functional Assays ◽  
Neutral Amino Acid Transporter ◽  
Acid Transporter ◽  
Pharmacologically Active

SLC6A19 (B0AT1) is a neutral amino acid transporter, the loss of function of which results in Hartnup disease. SLC6A19 is also believed to have an important role in amino acid homeostasis, diabetes, and weight control. A small-molecule inhibitor of human SLC6A19 (hSLC6A19) was identified using two functional cell-based assays: a fluorescence imaging plate reader (FLIPR) membrane potential (FMP) assay and a stable isotope-labeled neutral amino acid uptake assay. A diverse collection of 3440 pharmacologically active compounds from the Microsource Spectrum and Tocriscreen collections were tested at 10 µM in both assays using MDCK cells stably expressing hSLC6A19 and its obligatory subunit, TMEM27. Compounds that inhibited SLC6A19 activity in both assays were further confirmed for activity and selectivity and characterized for potency in functional assays against hSLC6A19 and related transporters. A single compound, cinromide, was found to robustly, selectively, and reproducibly inhibit SLC6A19 in all functional assays. Structurally related analogs of cinromide were tested to demonstrate structure–activity relationship (SAR). The assays described here are suitable for carrying out high-throughput screening campaigns to identify modulators of SLC6A19.

scholarly journals The Golgi CMP-sialic acid transporter: A new CHO mutant provides functional insights

Glycobiology ◽  
2008 ◽  
Vol 18 (11) ◽  
pp. 851-860 ◽  
Author(s):  
S. F. Lim ◽  
M. M. Lee ◽  
P. Zhang ◽  
Z. Song
Keyword(s):  
Sialic Acid ◽  
Acid Transporter

scholarly journals The Lysosomal Sialic Acid Transporter Sialin Is Required for Normal CNS Myelination

2009 ◽  
Vol 29 (49) ◽  
pp. 15355-15365 ◽  
Author(s):  
L. M. Prolo ◽  
H. Vogel ◽  
R. J. Reimer
Keyword(s):  
Sialic Acid ◽  
Acid Transporter ◽  
Cns Myelination

scholarly journals Hepatitis D Virus Entry Inhibitors Based on Repurposing Intestinal Bile Acid Reabsorption Inhibitors

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 666
Author(s):  
Michael Kirstgen ◽  
Kira Alessandra Alicia Theresa Lowjaga ◽  
Simon Franz Müller ◽  
Nora Goldmann ◽  
Felix Lehmann ◽  
...  
Keyword(s):  
Bile Acid ◽  
Taurocholic Acid ◽  
Hek293 Cells ◽  
Acid Uptake ◽  
Hepatitis D ◽  
Entry Inhibitors ◽  
Ic50 Values ◽  
Bile Acid Transporter ◽  
Acid Transporter

Identification of Na+/taurocholate co-transporting polypeptide (NTCP) as high-affinity hepatic entry receptor for the Hepatitis B and D viruses (HBV/HDV) opened the field for target-based development of cell-entry inhibitors. However, most of the HBV/HDV entry inhibitors identified so far also interfere with the physiological bile acid transporter function of NTCP. The present study aimed to identify more virus-selective inhibitors of NTCP by screening of 87 propanolamine derivatives from the former development of intestinal bile acid reabsorption inhibitors (BARIs), which interact with the NTCP-homologous intestinal apical sodium-dependent bile acid transporter (ASBT). In NTCP-HEK293 cells, the ability of these compounds to block the HBV/HDV-derived preS1-peptide binding to NTCP (virus receptor function) as well as the taurocholic acid transport via NTCP (bile acid transporter function) were analyzed in parallel. Hits were subsequently validated by performing in vitro HDV infection experiments in NTCP-HepG2 cells. The most potent compounds S985852, A000295231, and S973509 showed in vitro anti-HDV activities with IC50 values of 15, 40, and 70 µM, respectively, while the taurocholic acid uptake inhibition occurred at much higher IC50 values of 24, 780, and 490 µM, respectively. In conclusion, repurposing of compounds from the BARI class as novel HBV/HDV entry inhibitors seems possible and even enables certain virus selectivity based on structure-activity relationships.

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