Abstract
A peptide‐drug conjugate (PDC) is a single molecule formed by one or more drug molecules that are conjugated with functional short peptides. Some specially designed PDC can construct self‐delivering supramolecular nanomedicine and improve the therapeutic effect. The design and synthesis of novel PDCs with unique assembly behavior are important for the drug delivery system. Rhein is a natural product extracted from rhubarb and has extensive pharmacological properties. In the present work, we successfully synthesized a novel PDC (VKVK‐rhein) based on rhein through solid‐phase synthesis technology and conventional coupling chemical methods. The anthraquinone structure of rhein and the structure of the short peptide (VKVK, Val‐Lys‐Val‐Lys) provided VKVK‐rhein with special assembly properties. VKVK‐rhein can be assembled into supramolecular nanofibers in water. The equilibrium solubility, oil‐water distribution coefficient, zeta potential, and cell viability of VKVK‐rhein were systematically studied. Our work lays a foundation for further biological application of rhein‐based PDCs.
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