Intramolecular ditryptophan crosslinks enforce two types of antiparallel β structures Original Research Article

Abstract 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 –CONH2 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 –CONMe2 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. Article Outline