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Control of ditryptophan cross‐linking: dihydrotryptophan as a tryptophan precursor in peptide synthesis

1999; Wiley; Volume: 53; Issue: 4 Linguagem: Inglês

10.1034/j.1399-3011.1999.00044.x

1399-3011

T.D. Dinh, David L. Van Vranken,

Supramolecular Self-Assembly in Materials

Abstract: 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 γ S and γ R diastereomers and the indoline nitrogen was protected with a Cbz group. The resulting amino acid, N α ‐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.