Control of ditryptophan crosslinking: dihydrotryptophan as a tryptophan precursor in peptide synthesis

被引:10
作者
Dinh, TD [1 ]
Van Vranken, DL [1 ]
机构
[1] Univ Calif Irvine, Dept Chem, Irvine, CA 92697 USA
来源
JOURNAL OF PEPTIDE RESEARCH | 1999年 / 53卷 / 04期
关键词
tryptophan; protection; dihydrotryptophan; ditryptophan; tryptophan dimer;
D O I
10.1034/j.1399-3011.1999.00044.x
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
In neat trifluoroacetic acid, tryptophan side chains cross-link to form a diastereomeric mixture of tryptophan dimers. Convergent oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) converts tryptophan dimers to ditryptophan. Since cross-link formation is under thermodynamic control, there has been no simple way of controlling the regiochemistry of the cross-linking process when more than one tryptophan side chain is present. Here, we show that dihydrotryptophan (Dht) can be incorporated into peptides as a tryptophan precursor, which reforms tryptophan upon treatment with DDQ. Dihydrotryptophan was prepared as a mixture of gamma S and gamma R diastereomers and the indoline nitrogen was protected with a Cbz group. The resulting amino acid, N-alpha-BOC-Dht(Cbz)-OH, was then incorporated into peptides as a mixture of diastereomers. Dht was resistant to tryptophan cross-linking in neat trifluoroacetic acid and was converted back to tryptophan during convergent oxidation of tryptophan dimers. While Dht is useful for control of ditryptophan regiochemistry and as a potential tryptophan analog, it is not a general strategy for Trp protection since DDQ is unlikely to be compatible with easily oxidized amino acids such as cysteine.
引用
收藏
页码:465 / 474
页数:10
相关论文
共 24 条