Patent ID: 7517849
Filing Date: 2009-04-14
Classification: A61K,C07K,Y02A

Abstract:
1. An isolated ATP-binding cassette (ABC) transporter protein-inhibiting peptide, wherein (a) said ABC transporter protein comprises a sequence of amino acid residues which forms a plurality of transmembrane domains and extracellular domains when said protein is present in a cell plasma membrane, (b) said ABC transporter protein-inhibiting peptide has a first end and a second end, and said peptide has at said first end a group that is negatively charged under physiological conditions and at said second end has a group that is neutrally charged under physiological conditions; (c) said first end comprises 1 to 6 amino acid residues, of which at least 1 is negatively charged at physiological pH; (d) said second end consists of a sequence of amino acid residues, which sequence (i) consists of the sequence of amino acid residues of a transmembrane domain of said ABC transporter protein, and, optionally, further comprises between said first and second ends, one or more residues from the amino acid residue sequence of the extracellular domain of said ABC transporter protein directly adjacent to said transmembrane domain, (ii) consists of the sequence of ten or more amino acid residues of said transmembrane domain and, optionally, further comprises between said first and second ends, one or more residues from the amino acid residue sequence of the extracellular domain of said ABC transporter protein directly adjacent to said transmembrane domain or, (iii) consists of a sequence with at least 90% sequence identity to the sequence of (i) or (ii); (e) said peptide spontaneously inserts into a plasma membrane of a cell in the same orientation as the ABC transporter protein transmembrane domain with which it shares sequence identity when said ABC transporter protein is present in said plasma membrane of said cell; and (f) said peptide inhibits efflux of a substrate of said ABC transporter protein from cells expressing said ABC transporter protein when said cells are contacted with said peptide.