Intramolecular ditryptophan crosslinks enforce two types of antiparallel β structures

Background: Two types of biaryl crosslinks can be formed with natural protein sidechains: ditryptophan and dityrosine. Biaryl crosslinks have the same topology as disulfide crosslinks, yet little is known about their effect on local peptide structure. Results: Three ditryptophan-linked peptide dimers based on the sequence Ac-Leu-Trp-Ala-COX were prepared. The tripeptide dimer with –CONH 2 termini was too insoluble to study, but the tripeptide dimer with –COOMe termini crystallized from methanol/chloroform as an antiparallel β-sheet. The tripeptide dimer with a –CONMe 2 termini adopted a slipped antiparallel β structure in methanol/chloroform. Conclusions: These results suggest that intermolecular ditryptophan crosslinks that join the middle of peptide chains can confer a preference for antiparallel β-sheet structure. The effect is most dramatic when both the inside and outside edges of the dimer can form hydrogen bonds as in the crystal structure of dimer 3b .