Development of efficient synthetic methods for peptides and syntheses of self-defense peptides possessing anti-virus activity

点击翻译按钮获取中文摘要

Development of the solid-phase techniques for peptide synthesis have facilitated the syntheses of peptides, especially small and less complicated peptides. However, syntheses of large and/or multi disulfide containing-peptides have been encountered with some dufficulties, one being difficulties of final product purification due to the contamination of a number of deletion peptides and the other difficulties of controling egioselectivity of multi-disulfide bond formation. In order to circumvent these problems, we have developed new synthetic methodologies involving a affinity-purification method compatible with solid-phase peptide synthesis and disulfide bond-forming methods for peptides difficult to be solved in aqueous solvents which were utilized generally for disulfide bond formation.1.Development of the affinity-purification method utilizing the avidin-biotin system have been achieved. This methodology would facilitate the purification of peptides synthesized by solid-phase techniques.2.New cysteine S-protecting group (2-quinolinylmethyl) have been developed. The peptide bearing this protecting groups can be converted to the corresponding cystine peptide in DMF without solubility problem.3.We have investigated the feasibility of DMSO-mediated disulfide bond-forming reaction by formation of two-disulfide bond of apamin. And the new disulfide bond-forming reaction using AgOTf-DMSO/HCI system have been developed.4.Based on the above findings, we have achieved the syntheses of self-defense peptides [protegrins (18 aa, 2 S-S) and defensins (29-34 aa, 3 S-S) ] .