Chemical modifications of proteins which induce new receptor spe

Details Chemical modifications of proteins which induce new receptor spe Chemical modifications of proteins which induce new receptor spe

1980-10-23

1982-10-26

Rosen, Sam

Chemistry of carbon compounds

Miscellaneous organic carbon compounds

C-metal

C07G 700

Patent

active

043561179

ABSTRACT:
A new reagent effective in inhibiting cholesterol synthesis 75% in human fibroblasts derived from patients suffering from the disease familial hypercholestrolemia is mannose-6-phosphate-low density lipoprotein and is effective in tissue culture test systems at 100 .mu.g/ml after a ten-hour exposure. The broad purpose of this invention is to modify the receptor specificity of a protein so that it will enter cells which were previously impermeable and exert new effects or reverse a pathological condition. Toxins may also be modified in this manner producing cell type specific and tumor suppressive reagents which are effective in a dose range of 0.3-3 .mu.g. The object here is to use the reagent to selectively kill one cell type which is exerting a pathological effect without affecting normal cells. Among others to which this invention is applicable are Man6P-low density lipoprotein, Man6P-ricin, Man6P-Modeccin, anti Thy 1.2 monoclonal antibody-ricin and anti Thy 1.1 monoclonal antibody-ricin.

REFERENCES:
Olsnes et al.--Chem. Abst., vol. 93 (1980), p. 1892z.
Olsnes et al.--Chem. Abst., vol. 89 (1978), p. 102292b.
Eiklid et al.--Chem. Abst., vol. 93 (1980), p. 39052p.
Biochem. Biophys. Res. Commun., 45:622-628, 1971, Rogers et al.
Stowell et al., J. Biol. Chem., 253:6107-6110, 1978.
Chang et al., J. Biol. Chem., 252:1505-1514, 252:1515-1522, 1977.
Oeltmann et al., J. Biol. Chem., 254:1028-1032, 1979.
Refsnes et al., J. Exp. Med., 143:1464-1474, 1976.
Fodstad et al., Brit. J. Cancer, 34:418-425, 1976.

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