Binding of polyamides to proteins having SH3 or WW domains
OwnerRichard D. Tanaka, Paul J. Simpsoninventors
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Abstract
Polyamides having heteroaromatic amino acid moieties (especially pyrrole amino acid and/or imidazole amino acid moieties) form complexes with proteins having SH3 or WW domains. As a result of complex formation, the biological activity of such proteins can be inhibited.
Claims33
A method of forming a complex between a protein having an SH3 or a WW domain and a polyamide, comprising bringing together, under complex forming conditions, a protein having an SH3 or a WW domain and a polyamide comprising at least two heteroaromatic amino acid moieties —NH—Het—C(═O)—, where Het is a heteroaromatic moiety separating the —NH— and —C(═O)— groups by two or more atoms.
A complex between an SH3 or WW domain containing protein and a polyamide comprising at least two heteroaromatic amino acid moieties —NH—Het—C(═O)—, where Het is a heteroaromatic moiety separating the —NH— and —C(═O)— groups by two or more atoms.
A method of modulating the biological activity of an SH3- or a WW-domain containing protein, comprising contacting the protein with a complex-forming amount of a polyamide comprising at least two heteroaromatic amino acid moieties —NH—Het—C(═O)—, where Het is a heteroaromatic moiety separating the —NH— and —C(═O)— groups by two or more atoms, thereby modulating the biological activity of the protein.
A method of screening a library of compounds for the presence of a compound having affinity for an SH3 or a WW domain in a protein, comprising:
- (a) contacting a library of compounds with a protein having an SH3 or a WW domain and a complex-forming amount of a polyamide comprising at least two heteroaromatic amino acid moieties —NH—Het—C(═O)—, where Het is a heteroaromatic moiety separating the —NH— and —C(═O)— groups by two or more atoms, the polyamide being capable of forming a complex with the protein;
- and
- (b) comparing the amount of binding of the polyamide to the protein in absence of the library to the amount of the binding of the polyamide to the protein in the presence of the library.
Dependencies are inferred from the claim text.