Generation and Application\nof All Possible Conformations\nof Cyclic Tryptophan within and beyond Post-translational Modification

Isoprenylation\nof the indole C3-position of tryptophan accompanied\nby cyclization (c-Trp) is one of the most attractive post-translational\nmodifications because of C–C bond formation and drastic conformational\nalteration. As the modification generates two stereoisomers of the\n6/5/5-fused ring system and consequently, a mixture of four possible\nconformations as considered in proline, it is expected to influence\nthe biological activity in <i>Bacillus</i> quorum sensing\npheromone ComX containing the c-Trp residue. In this study, the simultaneous\ncontrol of the amide <i>cis–trans</i> equilibrium\nand pyrrolidine ring puckering was achieved by utilizing an N-carbamoylated\nand α-methylated 6/5/5-fused ring system. Furthermore, the conformationally\ndefined tripeptides containing the c-Trp residue were utilized to\nexamine the relationship between the biological activity and the conformation\nof the ComX pheromone. Several mimics showed high bioactivity, and\n more biologically active ComX mimics were created to reinforce the\nCH-π interaction of the c-Trp and the adjacent aromatic residue.