Chemical modifications of proteins which induce new receptor specificities and therefore elicit new effects in cells

摘要

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 &mgr; 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 &mgr;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.