Inhibition of cell proliferation and dihydrofolate reductase by liposomes containing methotrexate-dimyristoylphosphatidylethanolamine derivatives and by the glycerophosphorylethanolamine analogs.

@article{Hashimoto1985InhibitionOC,
  title={Inhibition of cell proliferation and dihydrofolate reductase by liposomes containing methotrexate-dimyristoylphosphatidylethanolamine derivatives and by the glycerophosphorylethanolamine analogs.},
  author={K Hashimoto and Joan E. Loader and M. Knight and Stephen C. Kinsky},
  journal={Biochimica et biophysica acta},
  year={1985},
  volume={816 1},
  pages={
          169-78
        }
}
Liposomes, which were prepared with the three methotrexate (MTX)-dimyristoylphosphatidylethanolamine (DMPE) derivatives described in the preceding paper, were tested for their ability to block proliferation of mouse 3T3 and L1210 cells. Tritiated deoxyuridine incorporation into DNA could be completely inhibited by liposomes sensitized with MTX-DMPE I (MTX-gamma-DMPE). Under similar conditions, liposomes containing MTX-DMPE II (MTX-alpha-DMPE) and MTX-DMPE III (MTX-alpha, gamma-diDMPE) produced… Expand
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TLDR
Three (I-III) methotrexate derivatives of dimyristoylphosphatidylethanolamine by conjugation of the alpha and/or gamma glutamyl carboxyl groups of the drug with the amino function of the phospholipid are synthesized. Expand
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Synthesis and characterization of methotrexate-dimyristoylphosphatidylethanolamine derivatives and the glycerophosphorylethanolamine analogs.
TLDR
Three (I-III) methotrexate derivatives of dimyristoylphosphatidylethanolamine by conjugation of the alpha and/or gamma glutamyl carboxyl groups of the drug with the amino function of the phospholipid are synthesized. Expand
Affinity labeling of the 5-methyltetrahydrofolate/methotrexate transport protein of L1210 cells by treatment with an N-hydroxysuccinimide ester of [3H]methotrexate.
TLDR
An N-hydroxysuccinimide ester of [3H]methotrexate has been employed to covalently label a specific binding protein that resides in the plasma membrane of L1210 cells, supporting a role for this protein in methotrexate transport. Expand
Structural requirements for anion substrates of the methotrexate transport system in L1210 cells.
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Results support the hypothesis that methotrexate transport proceeds via an anion-exchange mechanism and provide evidence that anion substrates for this system can be identified by their ability to promote metotrexate efflux. Expand
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TLDR
Methotrexate inhibits cellular proliferation by blocking formyl tetrahydrofolate (THF) production and covalently coupled to Staphylococcus aureus protein A bound specifically in vitro to cells pre‐incubated with relevant monoclonal antibodies, allowing the recovery of either a small proportion of cells not bearing a given antigen, or a smallportion of cells bearing agiven antigen, from heterogeneous cell populations. Expand
Cell-specific drug transfer from liposomes bearing monoclonal antibodies
TLDR
The techniques described here provide a simple quantitative assay for the ‘endocytic potential’ of any cell-surface determinant for which a ligand, such as an antibody or hormone, is available. Expand
Specific interaction of myeloma tumor cells with hapten-bearing liposomes containing methotrexate and carboxyfluorescein.
TLDR
Hapten-bearing liposomes containing methotrexate and the fluorescent solute carboxyfluorescein were incubated with murine myeloma tumor cells expressing surface immunoglobulin with affinity for the hapten and showed a patchy surface pattern, indicating intact liposome at the cell surface. Expand
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TLDR
The demonstration of multiple routes for methotrexate efflux and their differential sensitivities to alterations in energy metabolism thus provides a basis for explaining previously described asymmetries between the influx and efflux of metotrexate in mouse leukemia cells. Expand
Improved purification of tetrahydrofolate dehydrogenase from L1210 leukemia by affinity chromatography.
TLDR
Tetrahydrofolate dehydrogenase from a high enzyme mutant of L1210 mouse leukemia was purified to homogeneity by a simple two step procedure involving pH 5.1 and affinity chromatography employing a methotrexate-agarose column. Expand
Syntheses of alpha- and gamma-substituted amides, peptides, and esters of methotrexate and their evaluation as inhibitors of folate metabolism.
TLDR
Biochemical-pharmacological studies on the prepared compounds aided in establishing that the alpha- carboxyl grouping of the glutamate moiety contributes to the binding of MTX to dihydrofolate reductase while the gamma-carboxyl does not. Expand
Interactions of immunoliposomes with target cells.
TLDR
It is suggested that immunoliposome binding to the target cell surface is the primary uptake event at 4 degrees C and that the surface-bound liposomes are rapidly internalized by the cells at 37 degrees C, probably via an endocytic pathway. Expand
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