Synthesis of α-cyclic tripeptide ＆ tetrapeptide with potential bioactivity

• Main Authors: Chia-Wei Wong, 翁嘉偉
• Other Authors: Dar-Fu Tai
• Format: Others
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/6rn846

碩士 === 國立東華大學 === 化學系 === 103 === Cyclic peptide is a special class of peptide with broad-ranging biological activities. Compare to linear peptide, cyclic peptide is much more resistant to proteases hydrolysis due to its cyclic structure. Synthetic limitation of cyclic tripeptide and tetrapeptide are also owing to their rigid structure. The primary hurdle for cyclization is to bring the N- and C- termini of the linear peptide into close spatial proximity. Therefore, cyclization of a short linear precursor frequently results in the formation of cyclic dimer, rather than the desired cyclic monomer. Cyclic tetrapeptide has generated great interest because of their unique and potent biological activities. In this thesis, difficult cyclization was avoided by selecting a known sequence of tetrapeptide Ser-Gly-Ser-His from trypsin. Side chain protected tetrapeptide was synthesized by solution phase method and cyclized smoothly to give cyclo(L-Ser(Bn)-Gly-L-Ser(Bn)-L-His(Bn)). It was then characterized by NMR, IR and Mass spectrum and can be used for studying its biological activity. Second, the synthesis of the reported natural α-cyclic tripeptide, cyclo(glycyl-L-prolyl-L-glutamyl)) was carried out. It was first isolated from the Ruegeria strain of marine bacteria and possesses moderate bactericidal activity against Bacillus subtilis. This cyclic tripeptide was synthesized by solution phase method and characterized using NMR, IR and high resolution Mass. However, the spectra our cyclic tripeptide is not the same as reported in the literature. Surprisingly, we found the reported nature occurring antibiotic is actually a cyclic hexapeptide.