1995 Fiscal Year Final Research Report Summary
Syntheses of Big-Molecular-Form Sulfated Peptide Hormones Using Novel Synthetic Strategy
| Project/Area Number |
06672101
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Chemical pharmacy
|
|---|
| Research Institution | Niigata College of Pharmacy |
|---|
Principal Investigator |
KITAGAWA Kouki Faculty of Pharmaceutical Sciences, Niigata College of Pharmacy Professor, 薬学部, 教授 (60093853)
|
|---|
| Project Period (FY) |
1994 – 1995
|
| Keywords | Chemical Synthesis / Solid-Phase Peptide Synthesis / O-Sulfated Tyrosine / O-Sulfated Tyrosine Containing Peptide / Gastro-Intestimal Peptide Hormone / Gastrin / Cholecystokinin / Mass Spectrometry |
|---|
| Research Abstract |
1.A novel approach for the synthesis of tyrosine-sulfate containing peptides, in which the safety-catch-type protecting groups were effectively employed, was developed and reviewed in the "Journal of Synthetic Organic Chemistry in Japan".
2.A solid-phase method for the preparation of the peptide fragments protected with the safety-catch-type protecting groups was newly developed. Magainin-like antimicrobial peptide was synthesized by the solid-phase fragment condensation approach using the protected fragments bearing the safety-catch-type protecting groups.
3.Using a fragment condensation approach on the solid-support, the fully protected peptide corresponding to human big gastrin (34 amino acid residue) was effectively constructed. By the treatment of this peptide resin with 1M trimethylsilylbromide-thioanisole in TFA,human big gastrin (non-sulfate) was obtained in a reasonable purity. While by the treatment of the same resin with TFA,the peptide partially protected with the Msib/Msz protecting groups, the key intermediate for the sulfated big gastrin, was obtained. Conversion of this protected peptide to the sulfated peptide (big gastrin-II) is in progress.
4.Based on an extremely acid-labile 2-chlorotrityl resin and the critical deprotection method for the sulfated peptides, gastrin and cholecystokinin-related peptides were efficiently prepared. This approach can be extended as a highly efficient solid-phase synthetic approach for the direct preparation of the sulfated peptides.
5.Some useful information concerning the mass spectrum of the sulfated peptides were obtained through synthetic peptides prepared by our group.
|
