1994 Fiscal Year Final Research Report Summary
Development of efficient synthetic methods for peptides and syntheses of self-defense peptides possessing anti-virus activity
| Project/Area Number |
05671748
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
OTAKA Akira Kyoto Univ., Fac.Pharm.Sci., Assistant Professor, 薬学部, 助手 (20201973)
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| Co-Investigator(Kenkyū-buntansha) |
TAMAMURA Hirokazu Kyoto Univ., Fac.Pharm.Sci., Assistant Professor, 薬学部, 助手 (80217182)
FUJII Nobutaka Kyoto Univ., Fac.Pharm.Sci., Professor, 薬学部, 教授 (60109014)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Solid-phase synthesis / Disulfide bond / Self-defense peptide / Protegrin / Defensin / Avidin-biotin / Affinity purification |
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| Research Abstract |
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) ] .
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