Therapeutic peptides and diagnostic agents with their molecular size below the renal clearance threshold suffer from short blood circulation time. Here, we report a novel design of peptide-based ligand with a strong binding affinity to human serum albumin (HSA), which can be used as a tag to extend the blood circulation of small-size molecules. We designed ligands with dual alkyl groups connected with a negatively charged spacer. The ligands showed both higher binding affinity to HSA and a higher retention in mice blood than that of a single alkylated peptide.
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