Albumin-Binding Derivatives Of Therapeutic Peptides


Ontology type: sgo:Patent     


Patent Info

DATE

2005-09-29T00:00

AUTHORS

DOERWALD FLORENCIO ZARAGOZA , PESCHKE BERND

ABSTRACT

The present invention relates to a new drug delivery system, based on novel compounds with high affinity to plasma proteins (= affinity tags). These affinity tags can be linked to therapeutically active compounds and thereby enhance their half-life in plasma by reversible binding to plasma proteins.The present invention intends to provide a versatile delivery system for therapeutic agents, such as proteins, peptides, or small molecule drugs, by covalently binding these therapeutic agents to a plasma-protein ligand, capable of reversible binding to one or several plasma proteins. We have designed a novel linking strategy which enables the covalent binding of known, plasma-protein binding carboxylic acids to a broad variety of therapeutic peptides or proteins, or to any other type of compound, of which a prolonged periferal exposure at well-defined concentrations is required. This strategy consists in converting said plasma-protein binding carboxylic acid into a carboxylic acid mimetic, having a pKa between -5 and +7, in order to be ionized to a significant extent in plasma. Such a carboxylic acid mimetic could be, for instance, an N-acylsulfbnamide, which contains an additional functional group which enables covalent binding of the acid mimetic to a therapeutic agent. This linking strategy should not significantly disturb the structure of the plasma-protein binding acid, if a suitable acid mimetic has been chosen. The present invention álso relates to a compound of the general formula (II), wherein R1, G, Z, X, and Y are defined as described. The present invention also relates to pharmaceutical compositions comprising a compound according to the present invention and the use of compounds according to the present invention for preparing medicaments for treating disease. More... »

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