Synthesis and preliminary evaluation in vitro of novel naproxen-dendritic peptide conjugates

A series of bone-targeting prodrugs, dendritic L-Asp and L-Glu peptides Naproxen conjugates have been synthesized in a convergent approach and well characterized by NMR and MS techniques. Their solubility in water and hydroxyapatite affinity were evaluated in in vitro conditions. All the prodrugs were water soluble and exhibited high affinity to HAP. Compound NAP-G(2)-Asp was found more potent in HAP binding. The efficient release of the active drug moiety (naproxen) occurred by the cleavage of an amide bond in physiological conditions. These results indicated that the dendritic peptides might become a delivery system for bone tissues and provided an effective entry to the development of new bone-targeting molecules.