FIGURE 5. Structural models of the cyclotides caripe 1 and caripe 2.

(A) The sequence alignment of two novel cyclotides caripe 1 and 2 from Carapichea ipecacuanha is presented. The typical six cysteine residues are highlighted in yellow and are labeled with roman numerals and the six inter-cysteine loops are labeled on top of the alignment. Three-dimensional models of caripe 1 (B) and caripe 2 (C) show cyclotide-typical secondary structure elements, i.e., two anti-parallel β-sheets (in loops 4 + 5) and a helix (in loop 3). Surface representations of caripe 1 and caripe 2 are colored in hydrophobicity scale according to Eisenberg et al.,³⁹ to illustrate the amphiphilic nature of these peptides. Typical hydrophobic parts of cyclotides are loops 2 and 3, whereas the hydrophilic parts of the molecules can be found on the opposite site in loops 5 and 6. Representative amino acids, i.e., hydrophobic residues I3, F11 and V27 (caripe 1) and I2, F10 and V27 (caripe 2), as well hydrophilic residues P13 (caripe 1) and R12 (caripe 2) are labeled. The cyclotide models have been prepared using the CycloMod tool on CyBase and illustrations have been prepared with PyMol (see Materials and Methods section for details).