Claims
- 1. A method of delivering a biologically active amino-group-containing substance selectively to members of a cell population which comprises providing an acid-cleavable complex for controlled release of a biologically active amino-group-containing substance to a liquid medium, said complex comprising
- said amino-group-containing substance,
- a sulfide-linked substance comprising a cell binding-partner for a cell-surface receptor, and
- an acid cleavable linker between the sulfide-linked substance and the amino-group-containing substance, said complex comprising one of the two following units: ##STR6## where: one of X and Y is 0.sup.- ; the other of X and Y is the residue of the amino-group-containing substance whose amino nitrogen forms an amide link with a crbonyl group of the maleic acid function; Z is the sulfide-linked substance, including the sulfur of that link; R.sub.1 and R.sub.2 are independently selected from H and alkyl groups of C.sub.5 or less; and A is a bridge unit; and ##STR7## where X, Y, Z, R.sub.2, and A are as defined above, and s=2-5, and exposing the cells to said complex, whereby the complex is exposed to a pH low enough to hydrolyze the amide bond between the nitrogen of an amino group of the amino-group-containing substance and a carbonyl group of the maleic acid function of the cross-linked complex.
- 2. The method of claim 1 wherein A of the complex comprises the unit ##STR8## where R.sub.3, R.sub.4, R.sub.5, and R.sub.6 are independently selected from H, halogens, alkoxy and alkyl groups of C.sub.5 or less, and tertiary amines; and B is a linker to the maleimido function.
- 3. The method of claim 2 wherein R.sub.3, R.sub.4, R.sub.5, R.sub.6, and B are selected so that the sulfur attached to the aromatic ring of A has a pK.sub.a low enough in the corresponding thiophenol such that during formation of the sulfide group in A, competing reactions of OH.sup.- are avoided.
- 4. The method of claim 1 wherein the cell-binding partner is an antibody specific for a cell-surface antigen of a diseased cell, and the biologically active substance is a cytotoxic peptide.
- 5. The method of claim 1 where the antibody is transported across cell membranes containing the antigen, and the cross-linked complex is transported within the cell where the active substance is released at a cell site having a pH low enough to cleave the amide bond.
- 6. The method of claim 4 wherein the cell is a diseased cell and the active substance is a ribosome inactivating toxin.
Parent Case Info
This is a division of application Ser. No. 645,614 filed Aug. 29, 1984, and now U.S. Pat. No. 4,542,225.
BACKGROUND OF THE INVENTION
This invention was made with Government support. The Government has certain rights in this invention.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
4429008 |
Martin et al. |
Jan 1984 |
|
Non-Patent Literature Citations (3)
Entry |
Carlsson et al, Biochem. J., (1978), vol. 173, pp. 723-737, "Protein Thiolation and Reversible Protein-Protein Conjugation". |
Cleland, W. W. (1964) Bioch. 3:480. |
Shen and Ryser (1981) Biochem. and Biophys. Res. Commun. 102(3):1048-1054. |
Divisions (1)
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Number |
Date |
Country |
Parent |
645614 |
Aug 1984 |
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