Publications by authors named "Constantine M George"

2 Publications

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Biologics through chemistry: total synthesis of a proposed dual-acting vaccine targeting ovarian cancer by orchestration of oligosaccharide and polypeptide domains.

J Am Chem Soc 2009 Mar;131(11):4151-8

Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 YorkAVenue, New York, New York 10065, USA.

Carbohydrate and peptide-based antitumor vaccine constructs featuring clusters of both tumor associated carbohydrate antigens and mucin-like peptide epitopes have been designed, synthesized, and studied. The mucin-based epitopes are included to act, potentially, as T-cell epitopes in order to provoke a strong immune response. Hopefully the vaccine will simulate cell surface architecture, thereby provoking levels of immunity against cancer cell types displaying such characteristics. With this central idea in mind, we designed a new vaccine type against ovarian cancer. Following advances in glycohistology, our design is based on clusters of Gb(3) antigen and also incorporates a MUC5AC peptide epitope. The vaccine is among the most complex targeted constructs to be assembled by chemical synthesis to date. The strategy for the synthesis employed a Gb(3)-MUC5AC thioester cassette as a key building block. Syntheses of both nonconjugate and KLH-conjugated vaccines constructs have been accomplished.
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http://dx.doi.org/10.1021/ja810147jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2679991PMC
March 2009

Epithelial sodium channel is regulated by SNAP-23/syntaxin 1A interplay.

Biochem Biophys Res Commun 2006 May 24;343(4):1279-85. Epub 2006 Mar 24.

Center for Cell and Molecular Biology, Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, NJ 07030, USA.

Sodium-selective amiloride-sensitive epithelial channel (ENaC) located in the apical membrane is involved in the reabsorption of sodium in tight epithelia. The soluble N-ethylmaleimide-sensitive attachment receptors (SNAREs) mediate vesicle trafficking in a variety of cell systems. Syntaxin (a t-SNARE) has been shown to interact with and functionally regulate a number of ion channels including ENaC. In this study, we investigated the role of SNAP-23, another SNARE protein, on ENaC activity in the HT-29 colonic epithelial cell system and Xenopus oocytes. Recording of amiloride-sensitive currents in both systems suggest that SNAP-23 modulates channel function, though a much higher concentration is required to inhibit ENaC in Xenopus oocytes. The introduction of Botulinum toxin A (a neurotoxin which cleaves SNAP-23), but not Botulinum toxin B or heat-inactivated Botulinum toxin A, reversed the inhibitory effect of SNAP-23 on amiloride-sensitive currents. However, syntaxin 1A and SNAP-23 combined portray a complex scenario that suggests that this channel interacts within a quaternary complex. Synaptotagmin expression neither interacts with, nor showed any effect on amiloride-sensitive currents when co-expressed with ENaC. Pull down assays suggest mild interaction between ENaC and SNAP-23, which gets stronger in the presence of syntaxin 1A. Data further suggest that SNAP-23 possibly interacts with the N-terminal alphaENaC. These functional and biochemical approaches provide evidence for a complex relationship between ENaC and the exocytotic machinery. Our data suggest that SNARE protein interplay defines the fine regulation of sodium channel function.
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http://dx.doi.org/10.1016/j.bbrc.2006.03.093DOI Listing
May 2006