1987 Fiscal Year Final Research Report Summary
Synthetic Studies on Human Transforming Growth Factor(hTGF)-<alpha>
| Project/Area Number |
61570999
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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 |
FUJII Nobutaka Faculty of Pharmaceutical Sciences, Kyot University, 薬学部, 助教授 (60109014)
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| Co-Investigator(Kenkyū-buntansha) |
AKAJI Kenichi Faculty of Pharmaceutical Sciences, Kyoto University, 薬学部, 助手 (60142296)
FUNAKOSHI Susumu Faculty of pharmaceutical Sciences, Kyoto University, 薬学部, 助手 (10135593)
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| Project Period (FY) |
1986 – 1987
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| Keywords | human transforming growth factor-<alpha> / mitogenic factor / cancer cell growth / 1 M trimethylsilyl trifluoromethanesulfonate / トリフルオロメタンスルホン酸銀塩 |
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| Research Abstract |
In 1984, Derynck et al. deduced the primary structure of human TGF-<alph> consisting of 50 amino acid residues with three disulfide bridges by cDNA sequence analysis of it precursor. Because of great interests in biological role of this mitogenic factor associated with cancer cell growth, we undertook the synthesis of human TGF-<alph> both in solution phase and solid phase mehods.
1. Solution Phase Synthesis of human TGF-<alph>
A protected 50-residue peptide corresponding to the linear sequence of hTGF-<alpha> was prepared by azide condensations of nine peptide fragments of established purity. Amino acid derivatives bearing protecting groups removable by treatment with our newlydeveloped deprotecting reagent, 1 M trimethylsilyl trifluoromethanesulfonate (TMSOTf)/TFA, i.e., Asp(OChp)8 His(Bom), Glu(OBzl), Arg(Mts), Cys(Ad), Tyr(Cl_2-Bzl), Ser(Bzl), Lys(Z).
Final deprotection and air oxidation are under investigations.
2. Solid Phase Synthesis of Human TGF-<alpha>
By using Acm group for the protection of Cys, a 50-residue peptide with eptire sequence of hTGF-was assemhled onto the insoluble polymer support by the Boc-based solid phase procedure, After cleavage of the peptide from the rdsin by 1 M TMSOTf/TFA treatment, the resulting S-Acm derivative was converted to biologically active form by treatment with our newly developed Acm-deprotecting reagent, CF_3SO_3AG, followed by air oxidation.
In the mitogenic assay, our synthetic hTGF-<alpha> (10 ng/ml) exhibited the significant soft-agar-colony forming activity of NRK-cells in the presence of hTGF-<beta>.
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