Research Of Bone-targeting Aspartic Acid Oligopeptide And Derivatives Medicine

Bone diseases such as osteoporosis, bone cancer and osteoarthritis are familiar diseases in our life. It has been reported that osteoarthritis and rheumatoid arthritis were one of five diseases which were top exponential of influencing people health and consume in the further 25 years. Bone is a specific form of tissue which was hard rigidity and low penetrated in clinic therapy. To solve this problem, targeting therapy has been proposed, Bone-targeting carrier which have been developed in recent years was conjugated with drug, in order to improve the treatment of bone diseases.In this dissertation, A novel bone-targeting Nonsteroidal Antiinflammatory agents were designed through the conjugation of oligopeptide with Ibuprofen and Naproxen which were popular used in the clinic.According to literature, peptide which has the affinity to bone was related with the length of oligopeptide. We synthesize peptide (Asp)₅ and (Asp)₇ conjugated with Nonsteroidal Antiinflammatory Agents.It has been reported that small peptide (Asp)₆ was affinity to bone in 2000 and the article did not give the route of the synthesis, just indicated using the Solid-Phase organic synthesis. we design and chose a rational route of synthesize aspartic acid oligopeptide by Mixture anhydrides methods. L-Asp₆ was synthesize from L-Aspartic acid by 14 step with total yield of 6.61% . We study the method of prepare the peptide (Asp)₅ and (Asp)₇ conjugated with Nonsteroidal Antiinflammatory Agents and finally choose the DCC method to synthesize the two series of bone-targeting Nonsteroidal Antimflammatory Agents.The target compounds were tested through adsorption experiments of HA in vitro. The experiment results showed that the target compounds designed has good affinity to bone and the (Asp)₆- Naproxen was the best.In conclusion, 31 compounds were synthesized, including 25 new compounds and 7 target compounds, their structures were characterized by ¹H-NMR and MS. The adsorption experiment showed the designed aim compounds had strong affinity to bone.