Study On Synthesis And Self-assembly Of The Cyclic Hexapeptide

Cyclic peptide nanotube is one of organic nanotubes owning distinctive advantage,because of its unique structure and properties.It possesses potential application value in the fields of chemistry,biology,material sciences and medical science.In this paper,the systhesis and the self-assembly of hexapeptide containing ?-amino acid were studied.The author of dissertation follows the basic principles for cyclic peptide nanotubes designing,combines the structure typle of the cyclic peptide molecules,designing two typles of ?-cyclic hexapeptides.By introducing ?,?-amino acid alternately to form the basic framework of the hexapeptide,by introducing cis-?-aminocyclopentyl or ?-aminocyclohexanecarboxylic acid,the rigidity of the macrocyclic peptide system is increased so that the formed cyclic peptide skeleton is almost The configuration of the plane.The optical activity ?-amino acid was successfully synthesized by the addition of lactone of cycloalkene,elimination of halogenated hydrocarbons,azidation,reduction,protection of amino groups and resolution of enantiomers,named by(1R,3S)-Boc-?-aminocyclohexylcarboxylic acid.In the presence of 1,3-cyclopentadiene and p-toluenesulfonyl nitrile,the bridging compound was formed by Diels-Alder reaction.The bridged ring compound is hydrolyzed in dilute acid solution to give cis-?-3-amino-4-cyclopentenecarboxylic acid.The later compound was protected by Boc and then by resolution of enantiomers.Another optically active ?-amino acid was obtained:(1R,3S)-Boc-?-aminocyclopentylcarboxylic acid.Based on the above work,(1R,3S)-Boc-?-aminocyclopentylcarboxylic acid,(1R,3S)-Boc-?-aminocyclohexylcarboxylic acid,L-phenylalanine,L-(N'-Cbz)-Liramine as raw material,Boc-strategy was used in the liquid phase,and two kinds of ?,?-amino acid alternating ring hexapeptide TM-1 and TM-2 were successfully synthesized by one by one method.And the method of synthesizing chain polypeptide and cyclic hexapeptide containing cyclic ?-amino acid was studied.The planarity of cyclic peptides is the primary factor affecting the self-assembly of cyclic peptide nanotubes.In the cyclic peptide skeleton,cis-?-aminocyclopentane or cyclohexanecarboxylic acid is introduced so that the formed cyclic peptide skeleton takes almost the same planar configuration.In(1R,3S)-Boc-?-aminocyclohexylcarboxylic acid and(1R,3S)-Boc-?-aminocyclopentylcarboxylic acid molecular,the skeleton of the ring takes a chair conformational,and the ?-amino acid and the ?-amino acid are alternately linked so that The cyclic peptide skeleton is almost on the same plane,and the amide C = O and NH are approximately perpendicular to the macrocyclic plane,which facilitates the self-assembly of the cyclic peptide molecules to form the cyclic peptide nanotubes.Therefor,cyclic peptide backbone interactions form a cyclic peptide self-assembly of nanotubes easily.L-(N'-Cbz)-lysine has multiple functional groups that can regulate the surface properties of cyclic peptide nanotubes by lysine introduction of side chains.In this paper,the synthetic target molecule TM-1 was self-assembled.The assembly was characterized by SEM and TEM.The results show that the main driving force for self-assembly is hydrogen bonding of cyclic peptide melecules.