Acid-cleavable compound
AssigneeDana-Farber Cancer Institute, Inc.
InventorsWalter A. Blattler, John M. Lambert, Peter D. Senter
Life of this patent
Estimating the term…
Abstract
Amino-sulfhydryl cross-linking reagents that are cleavable under mildly acidic conditions are disclosed. Also disclosed are methods of making the cross-linkers, as well as methods of using the cross-linkers, e.g., to deliver a biologically active substance across the membranes of selected cells in a heterogeneous cell population; once inside the cell the active substance is released, intact, by the transient, mild acidity of certain cell structures. Finally, a method of characterizing complex multi-chain protein structures is disclosed.
Claims20
An acid-cleavable complex for controlled release of an amino-group-containing substance to a liquid medium, said complex comprising
- said amino-group-containing substance
- a sulfide-linked substance, 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 carbonyl 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.
A cross-linking reagent suitable for forming an acid-cleavable cross-link between the amino nitrogen of an amino-group-containing substance and a substance containing a sulfhydryl function, said cross-linking reagent comprising one of the following units:
- ##STR12## where R.sub.1 and R.sub.2 are independently selected from H and alkyl groups of C.sub.5 or less, and A comprises a bridge unit;
- and ##STR13## where R.sub.2 and A are as defined above and s=2-5.
Dependencies are inferred from the claim text.