The Scripps Research Institute

University of Zürich

Birgit Dreier

Carlos F Barbas, Iii

Peter Sonderegger

Stefan Hettwer

Susanne Sales

Beat Kunz

Marc F Bolliger

Daniel Lüscher

Raymond Reif

The invention relates to a method for determining whether a compound is a neurotrypsin inhibitor, characterized in that the compound is incubated together with neurotrypsin, a variant thereof or a fragment comprising the protease domain and with a protein or peptide comprising agrin, a variant thereof or a fragment comprising the &#x3b1;- or the &#x3b2;-cleavage site of agrin, in an aqueous buffer solution, and the amount of cleavage of agrin is measured. Additionally, the invention relates to inhibitors of neurotrypsin found by this method, in particular to compounds of formula wherein Haland Halare fluorine, chlorine or bromine, and the use of such inhibitors for the treatment and/or prophylaxis of diseases caused by deficiency of synapses, for example skeletal muscle atrophy, schizophrenia, and cognitive disturbance.

Method for determining inhibitors of neurotrypsin

Polypeptides that contain zinc finger-nucleotide binding regions that bind to nucleotide sequences of the formula TNN are provided. Compositions containing a plurality of polypeptides, isolated heptapeptides possessing specific binding activity, polynucleotides that encode such polypeptides and methods of regulating gene expression with such polypeptides, compositions and polynucleotides are also provided.

Zinc finger binding domains for TNN

Polypeptides that contain from 2 to 12 zinc finger-nucleotide binding regions that bind to nucleotide sequences of the formula (ANN)2&#x2013;12 are provided. Polynucleotides that encode such polypeptides and methods of regulating gene expression with such polypeptides and polynucleotides are also provided.

Zinc finger binding domains for nucleotide sequence ANN

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Birgit Dreier