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., Cicero, D.o., Bianchi, E., Pessi, A., Bazzo, R. (1996). High resolution solution structure of two members of a conformationally homogneous combinatorial peptide library based on the classical zinc finger motif. JOURNAL OF BIOMOLECULAR NMR, 8, 36-48.

High resolution solution structure of two members of a conformationally homogneous combinatorial peptide library based on the classical zinc finger motif

CICERO, DANIEL OSCAR;
1996-01-01

Abstract

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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10
English
Barbato, G., Cicero, D.o., Bianchi, E., Pessi, A., Bazzo, R. (1996). High resolution solution structure of two members of a conformationally homogneous combinatorial peptide library based on the classical zinc finger motif. JOURNAL OF BIOMOLECULAR NMR, 8, 36-48.
Barbato, G; Cicero, Do; Bianchi, E; Pessi, A; Bazzo, R
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/87591
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