Receptor derived peptides as modulators of receptor activity
OwnerLennart Olsson, Tatjana Narandainventors
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Abstract
Oligopeptides having an amino acid sequence corresponding to a receptor's extracellular domain, and having sequence similarity to regulatory peptides from MHC class I antigens, enhance or replace the physiological response of ligand binding to the corresponding receptor. The oligopeptides are used in diagnosis and therapy of diseases that involve inadequate or inappropriate receptor response as well as in the screening of drug candidates that affect surface expression of receptors. Also useful for drug screening is a modified receptor molecule, where the sequence corresponding to the regulatory peptide is modified or deleted.
Claims36
An oligopeptide comprising at least about 8 amino acids and less than about 40 amino acids which has an amino acid sequence corresponding to the activation sequence of the extracellular domain of a cell surface receptor.
An oligopeptide selected from the group consisting of SEQ ID NO:2;
- SEQ ID NO:3;
- SEQ ID NO:4;
- SEQ ID NO:5;
- SEQ ID NO:6;
- SEQ ID NO:7;
- SEQ ID NO:8;
- SEQ ID NO:9;
- SEQ ID NO:10;
- SEQ ID NO:11;
- SEQ ID NO:12;
- SEQ ID NO:13;
- SEQ ID NO:14;
- SEQ ID NO:15;
- SEQ ID NO:16;
- SEQ ID NO:17;
- SEQ ID NO:18;
- SEQ ID NO:19;
- SEQ ID NO:20;
- SEQ ID NO:21;
- SEQ ID NO:22;
- SEQ ID NO:23;
- SEQ ID NO:24;
- SEQ ID NO:25;
- SEQ ID NO:26;
- SEQ ID NO:27;
- SEQ ID NO:28;
- SEQ ID NO:29;
- SEQ ID NO:30;
- SEQ ID NO:31;
- SEQ ID NO:32;
- SEQ ID NO:33;
- SEQ ID NO:34;
- and SEQ ID NO:35.
An oligopeptide at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NO:2;
- SEQ ID NO:3;
- SEQ ID NO:4;
- SEQ ID NO:5;
- SEQ ID NO:6;
- SEQ ID NO:7;
- SEQ ID NO:8;
- SEQ ID NO:9;
- SEQ ID NO:10;
- SEQ ID NO:11;
- SEQ ID NO:12;
- SEQ ID NO:13;
- SEQ ID NO:14;
- SEQ ID NO:15;
- SEQ ID NO:16;
- SEQ ID NO:17;
- SEQ ID NO:18;
- SEQ ID NO:19;
- SEQ ID NO:20;
- SEQ ID NO:21;
- SEQ ID NO:22;
- SEQ ID NO:23;
- SEQ ID NO:24;
- SEQ ID NO:25;
- SEQ ID NO:26;
- SEQ ID NO:27;
- SEQ ID NO:28;
- SEQ ID NO:29;
- SEQ ID NO:30;
- SEQ ID NO:31;
- SEQ ID NO:32;
- SEQ ID NO:33;
- SEQ ID NO:34;
- and SEQ ID NO:35.
A method of modulating the internalization of a cell-surface receptor containing an activation sequence comprising binding an exogeneous compound to said activation sequence.
A mammalian cell comprising a modified cell surface receptor, wherein said modification comprises an amino acid sequence substitution, insertion or deletion in an activation sequence of the region of the extracellular domain, and wherein said modified sequence is of at least about 8 amino acids and less than about 40 amino acids.
A method of determining an activation sequence of a cell surface receptor, said method comprising searching for a region of sequence similarity between said cell surface receptor and the sequence of an α1-domain of an MHC Class I antigen.
A method for screening for a bioactive agent capable of binding to the activation sequence of a cell surface receptor, said method comprising combining a cell surface receptor and a candidate bioactive agent, and determining the binding of said candidate agent to the the activation sequence of said cell surface receptor.
A method for screening for an bioactive agent capable of modulating the internalization of a type-1 cell-surface receptor, said method comprising the steps of:
- a) adding a ligand bound by said cell surface receptor and a candidate bioactive agent to a cell comprising said cell surface receptor;
- and
- b) determining the effect of the candidate bioactive agent on the internalization of said receptor.
A method for screening for an bioactive agent capable of modulating the internalization of a type-2 cell-surface receptor, said method comprising the steps of:
- a) adding a candidate bioactive agent to a cell comprising said cell surface receptor;
- and
- b) determining the effect of the candidate bioactive agent on the internalization of said receptor.
A composition comprising a cell-surface receptor with an exogeneous compound bound to the activation sequence.
Dependencies are inferred from the claim text.