1988 Fiscal Year Final Research Report Summary
Exploitation of a New Unsymmetrical Disulfide-Bonding Reaction and Its Application to the Synthesis of Cystine-Conatining Peptides
| Project/Area Number |
62470135
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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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 |
YAJIMA Haruaki Faculty of Pharmaceutical Sciences, Kyoto University, 薬学部, 教授 (00025678)
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| Co-Investigator(Kenkyū-buntansha) |
FUNAKOSHI Susumu Faculty of Pharmaceutical Sciences, Kyoto Universtiy, 薬学部, 助手 (10135593)
FUJII Nobutaka Faculty of Pharmaceutical Sciences, Kyoto University, 薬学部, 助教授 (60109014)
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| Project Period (FY) |
1987 – 1988
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| Keywords | Thallium (III) oxidation / Sulfoxide-directed disulfide bond forming reaction / Open-chain unsymmetrical cystine peptide / CGRP / Insulin |
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| Research Abstract |
Out present knoeledge dose not still allow routine synthesis of any complex peptide (protein) containing several disulfide bonds. This pertains to any peptide (protein) whether prepared by chemicalmethods or recombinant DNA methods. The hitherto employed air oxidation procedure for disulfide bond formation is not satisfactory, since it gives a considerable amount of ploymeric compounds and consequently reduces the final yield immensely.
In order to improve this situation, we have explored two new disulfide bonding reactions; i,e., (1) thallium (III) trifluoroacetate oxidation and (2) sulfoxidedirected disulfide bond forming reaction. By using thallium (III) oxidation, oxytocin, urotensin II, - and -human calcitonin gene-related peptide (CGRP) were synthesized. Usefulness of sulfoxide-directed disulfide bonding reaction was also demonstrated in the syntheses of chicken CGRP and a open-chain unsymmetrical cystine peptide, H-Cys-Ala-NH_2 H-Cys-Gly-OH.
In order ot demonstrate the usefulness of these two procedure for the synthesi of more complex peptides, human insulin and human relaxin consisting of A- and B- chains crosslinged with 3 S-S bonds were selected as the synthetic targets. The protected A- and B-chains of human insulin were synthesized by solution phase method, and those of human relaxin by the fmoc-based solid phase technique. Total syntheses of these two peptides by using the above two new disulfide bonding reactions are under investigations.
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