Site-specific Chemical Ligation of Native Human Serum Albumin as a Carrier for Drugs

Abstract

Researchers at the University of California, Davis, have developed a method to prepare chemically well-defined HSA-drug conjugates, such that ligation can occur in vitro or in vivo under physiological condition.

Full Description

Human serum albumin (HSA), the most abundant protein in human blood plasma, has long been recognized for its versatility in clinical applications. Its natural abundance, biocompatibility, and ability to bind various molecules make it an attractive platform for both diagnostic and therapeutic purposes. Clinically, HSA has been successfully employed as a non-covalent carrier in several approved drugs, including insulin (e.g., Levemir), GLP-1 analogs (e.g., Liraglutide), and chemotherapeutics (e.g., Abraxane). Despite these successes, attempts to develop HSA-based covalent drug conjugates have not yet resulted in any approved therapies, highlighting a gap in translating covalent HSA-drug conjugates into clinical use.

Using the one-bead-one-compound (OBOC) peptide library, researchers at the University of California Davis have discovered several reactive peptidomimetics that covalently bond and modify HSA. These acrylated-peptidomimetics conjugate HSA through Aza-Michael addition in a site-specific manner. Also, the peptidomimetics are compatible with the maleimide-based protein functionalization, enabling dual functionalization of HSA. Preliminary data in the laboratory indicate that HSA-based modifications may enable new treatment options for diabetes and certain cancers.

Applications

• Preparation of well-defined HSA-drug covalent conjugates for drug delivery.

Features/Benefits

• Use of biocompatible peptidomimetics scaffolds. 
• Can attach different payloads for specific drug targeting.

Patent Status

Patent Pending

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• Site-Specific Albumin-Selective Ligation to Human Serum Albumin under Physiological Conditions - 11/09/2022