Summary
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 α-helical portion of a 26-residue ‘consensus’ peptide (CP1) belonging to the Cys2-Hys2 zinc-finger family. The result was shown to be a highly homogeneous α-helical library (Bianchi et al., 1995). The structures of the parent compound (CP1) and of a representative member (CP1m) 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.
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Abbreviations
- t-Bu:
-
tert-butyloxycarbonyl
- Fmoc:
-
9-fluorenylmethoxycarbonyl
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Barbato, G., Cicero, D.O., Bianchi, E. et al. High-resolution solution structure of two members of a conformationally homogeneous combinatorial peptide library based on the classical zinc-finger motif. J Biomol NMR 8, 36–48 (1996). https://doi.org/10.1007/BF00198138
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DOI: https://doi.org/10.1007/BF00198138