| Cis-trans isomerization of amide bonds plays critical roles in protein molecular recognition, protein folding, protein misfolding and disease. Aromatic-proline sequences are particularly prone to exhibit cis amide bonds. The roles of residues adjacent to a tyrosine-proline residue pair on cis-trans isomerism were examined. A series of peptides XYPN was synthesized and the following effects were observed: (a) aromatic residues immediately preceding Tyr-Pro disfavor cis amide bonds; (b) proline residues preceding Tyr-Pro lead to multiple species; and (c) other residues exhibit similar values of Ktrans/cis. In addition, the effect of the i+3 residue was examined in a limited series of peptides TYPZ. NMR data indicated that aromatic residues, Pro, Asn, Ala and Val at the i+3 residue all favor cis amide bonds.; The zinc finger is a compact metal-binding motif, consisting of an N-terminal beta-hairpin and a C-terminal alpha-helix connected by a loop. A new, general lanthanide-binding motif inspired by zinc fingers was designed, which involved optimization of nearly all residues of the protein. A series of peptides was synthesized and analyzed by circular dichroism, and the dissociation constants were determined for each peptide. The optimized peptide design, LF4, bound Terbium (III) with a dissociation constant of 6.8 muM and adopted a metal-bound structure similar to a zinc finger.(Abstract shortened by UMI.)... |
