title: On the design of zinc-finger models with cyclic peptides bearing a linear tail.
abstract: Cyclic peptides with a linear tail (CPLT) have been successfully used to model two zinc fingers (ZFs) adopting the treble-clef- and loosened zinc-ribbon folds. In this article, we examine the factors that may influence the design of such ZF models: mutations in the sequence, size of the cycle, and size of the tail. For this purpose, several peptides derived from the CPLT-based models of the treble-clef- and loosened zinc-ribbon ZF were synthesized and studied. CPLT-based models appear to be robust toward mutations, accommodate various cycle sizes, and are sensible to the size of the linking region of the tail located between the cycle and the coordinating amino acids. Based on these criteria, we describe the design of a new CPLT-based model for the zinc-ribbon ZFs, LZR , and compare it to a linear analogue, LZR(lin) . The model complex Zn⋅LZR is able to fold correctly around the metal ion contrary to Zn⋅LZR(lin) , suggesting that CPLT-based models are more likely to yield structurally meaningful models of ZF sites than linear peptide models. Finally, we draw some rules that could allow the design of new CPLT-based metallopeptides with a controlled fold.
authors: Laboratoire de Chimie et Biologie des Métaux, Equipe de Physicochimie des Métaux en Biologie, UMR 5249 CNRS/CEA-DSV-iRTSV/, Université Joseph Fourier, 17 rue des Martyrs, Grenoble 38054, France.
authors: Aurélie
authors: A
authors: Jacques
authors: Bastien
authors: B
authors: Mettra
authors: Vincent
authors: V
authors: Lebrun
authors: Jean-Marc
authors: JM
authors: Latour
authors: Olivier
authors: O
authors: Sénèque
mesh_terms: D000595:Amino Acid Sequence; D009682:Magnetic Resonance Spectroscopy; D008667:Metalloproteins / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000737:chemistry*; D016335:Zinc Fingers
chemical_list: D008667:Metalloproteins; D010456:Peptides, Cyclic