The Design And Synthesis Of Caspase-3 Enzyme Inhibitor Cyclicpentapeptide

Caspase plays a key role in apoptosis.Caspase-3 is the specific implementers of apoptosis,and is eventual effector in Caspase-class chain reaction of apoptosis.Clarifying the mechanism of apoptosis in the molecular level is very important for discovering a new drugs of treating some diseases.According to homologous series and isostere principles of drug design,based on the structure and activities of Sansalvamide A cyclic peptide,new types of cyclic peptide containing aspartate,proline,L-2-naphthyl alanine,Leucine,Valin were design and synthesized in this paper.The inhibitor of Caspase-3 contained cyclic peptide has not been reported.In this paper,the preparation of unnature amino acid and the synthesis of chain peptide and cyclic peptide had been studied.The unnature amino acid was prepared.The linear peptide and the cyclic peptide were synthesized by one by one strategic.All new compounds were purified by recrystallization and chromato graphic.The structure of the line peptides and the target molecules were determined by NMR,MS.The process of synthesis:1)The 2-methylnaphthalene was treated as the starting material and after a series of reaction methyl acetyl-2-naphthylalanine methyl was obtained respectively.By biological hydrolysis the L-2-naphthylalanine was obtained.2)Boc-(?-benzyl ester)aspartate was prepared by treat of aspartate with esterification of carboxyl and carbonylation alkoxyphenyl of Amino.3)The five pentapeptide was synthesized by connecting amino acid one by one.At last,the target molecule was obtained through cycliczation of the unprotected linear pentapeptide under the alkaline conditions.