Inverse Solid Phase Synthesis Of Antitumor Peptide YSL、YSV And C-terminal Derivatives

YSL and YSV are two anti-tumor tripeptides obtained through high throughput screening. They have similar structures but different anti-tumor activity. YSL has potent Anti-hepatoma activity while YSV can strongly inhibit non-small cell lung cancer and Melanoma, so we consider modifying the third amino acid to synthesize new tripeptides with better anti-tumor activity.The thesis combines the advantages of Fmoc-SPPS and TAEC technology.By exploring and optimizing reaction conditions, improving traditional azide method and introducing high efficient coupling reagent HOCt, we developed a new method (Inverse Solid Phase Peptide Synthesis, ISPPS) to modify C-terminal of peptide and synthesize peptide from N terminal to C terminal. The reaction can be carried out at room temperature under mild conditions and be easily monitored, and the working-up is simple and efficient. This method is complementary to the direct solid phase peptide synthesis.Four parts of work were done in this thesis:(1) Explore appropriate methods to synthesize amino acids materials of ISPPS;(2) Design and synthesize rational linker to connect the Wang resin and N-terminal of peptide chain;(3) Synthesize anti-tumor peptide YSL, YSV and its derivatives YSA, YSI, YSF as well as all kinds of C-terminal derivatives by ISPPS in a simple and efficient way. All the compounds we synthesized have been confirmed by HPLC and MS.(4) Evaluate biological activity of several YSL derivatives by MTT method preliminarily.