Journal article
Biochemical characteristics, metabolism, and antitumor activity of several acetylated hexosamines
Journal of supramolecular structure, Vol.7(2), pp.235-250
1977
DOI: 10.1002/jss.400070208
PMID: 599936
Abstract
We have synthesized several potential inhibitors and/or modifiers of the carbohydrate portion of plasma membrane glycoconjugates. These include fluorinated and actylated analogs of D-glucosamine, D-galactosamine, and D-mannosamine. These compounds have been tested to determine their effects on both [14C]glucosamine and [3H]leucine incorporation into glycoconjugate and on cell growth and viability using P-288 murine lymphoma cells maintained in tissue culture. The most cytotoxic agent tested was 2-acetamido-2-deoxy-1,3,4,6-tetra-O-acetyl-β-D-glucopyranose or simply β-pentaacetylglucosamine which prevented cell growth at 10-4-10-3 M. β-Pentaacetylglucosamine cytotoxicity was correlated with its high lipid solubility, having an octanol/water partition coefficient of 0.424 as compared with 0.278 for the α-anomer and 0.017 for N-acetylglucosamine. In vitro metabolism studies with [14C]-and/or [3H]-labeled pentaacetylglucosamine have indicated intracellular de-O-acetylation leading to the biosynthesis of UDP-N-acetylglucosamine, followed by the incorporation of this sugar into cellular glycoprotein. Concomitant with the formation of increased amounts of this nucleotide sugar, intracellular UTP and CTP pools fell to one third normal within 3 h after the administration of 1 mM pentaacetylglucosamine. At present it is unclear whether the cytotoxicity of β-pentaacetylglucosamine or other similar agents is due to alterations in nucleotide and nucleotide-sugar pools causing a decrease in energy charge and polynucleotide biosynthesis or is due to a direct effect on membrane glycoconjugate biosynthesis.
Details
- Title: Subtitle
- Biochemical characteristics, metabolism, and antitumor activity of several acetylated hexosamines
- Creators
- R. J. Bernacki - Roswell Park Cancer InstituteM. Sharma - Roswell Park Cancer InstituteN. K. Porter - Roswell Park Cancer InstituteY. Rustum - Roswell Park Cancer InstituteB. Paul - Roswell Park Cancer InstituteW. Korytnyk - Roswell Park Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Journal of supramolecular structure, Vol.7(2), pp.235-250
- Publisher
- Alan R. Liss, Inc
- DOI
- 10.1002/jss.400070208
- PMID
- 599936
- ISSN
- 0091-7419
- eISSN
- 1547-9366
- Number of pages
- 16
- Language
- English
- Date published
- 1977
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359810102771
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