DESIGN, SYNTHESIS AND STRUCTURE OF A ZINC-FINGER WITH AN ARTIFICIAL BETA-TURN

We have incorporated a bicyclic beta-turn mimetic (BTD; beta-turn dipe ptide) into a zinc finger, creating a zinc finger with an artificial b eta-turn. The designed peptide chelates zinc and has the same fold as the unmodified native zinc finger (finger 3 of the human YY1 protein). A combination of H-1 NMR and structure calculations reveals that, in solution, this zinc finger has a fold similar to the known wild-type c rystal structure and to other zinc fingers containing the consensus se quence X-3-Cys-X-4-Cys-X-12-His-X-3-His-X. The peptide was designed wi th BTD between the chelating cysteine residues, with BTD forming a typ e II' beta-turn linking the two strands of a distorted anti-parallel b eta-sheet. The C-terminal portion of the peptide forms a helix with zi nc co-ordinating histidine residues on successive turns of the helix. This work represents a step towards developing methods by which parts of a target protein may be replaced by peptide mimetics. (C) 1998 Acad emic Press Limited.