Non-Covalent Albumin Ligands in FDA-Approved Therapeutic Peptides and Proteins

An increasing number of drugs that consist of a therapeutic peptide or protein linked to an albumin-binding structure are being approved. In this perspective, the pharmacokinetic data of currently marketed drugs of this type will be presented. Acylation with fatty acids or fatty α,ω-dicarboxylic acids has been used successfully to prepare long-acting analogs of insulin, GLP-1, and other peptides but not of larger proteins. With a tetrazole-sulfonylamide fatty acid bioisostere, it has now been possible to prepare a long-acting analog of human growth hormone (191 amino acids), which is suitable for once-weekly administration.