High-resolution solution structure of two members of a conformationally homogeneous combinatorial peptide library based on the classical zinc-finger motif.
We describe the high-resolution structure by NMR of two peptides that belong to a combinatorial library based on the zinc-finger motif. The library represents, to the best of our knowledge, the first example of a conformationally homogeneous peptide library and was obtained by introducing random residues in five positions of the alpha-helical portion of a 26-residue 'consensus' peptide (CP1) belonging to the Cys(2)-Hys2 zinc-finger family. The result was shown to be a highly homogeneous alpha-helical library (Bianchi et al., 1995). The structures of the parent compound (CPI) and of a representative member (CPlm) that was selected by screening the library with a monoclonal antibody are compared in detail as an example of the very high stability of the zinc-finger scaffold upon sequence variability. The two peptides exhibit an extremely high degree of structural similarity. The use of this type of conformationally constrained combinatorial library might represent a step forward in the design of peptidomimetics, as it considerably accelerates the process of the identification of the spatial relationship among the pharmacophoric groups.
Barbato
G
G
Department of Chemistry, Research Institute of Molecular Biology (IRBM), Pomezia, Rome, Italy.
Cicero
D O
DO
Bianchi
E
E
Pessi
A
A
Bazzo
R
R
D009682:Magnetic Resonance Spectroscopy; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D016335:Zinc Fingers
D019151:Peptide Library; D010455:Peptides