The present invention provides a family of peptides based upon the M2GlyR sequence. These peptides are derivatives of the M2GlyR sequence and can be modified at their ends to include a plurality of polar amino acid residues to enhance their solubility. Particularly preferred derivatives include portions of the M2GlyR sequence which are palindromic to another portion of the peptide or to the M2GlyR sequence itself. Preferably these portions are at least 7 amino acid residues in length. Peptides embraced by the present invention are characterized by having greater effects on the transepithelial electrical resistance of cells at lower concentrations. Peptides of the present invention have been shown to increase Isc in MDCK epithelial cell monolayers with half maximal effects observed at or below 30 Î¼M, a nearly 10-fold improvement over any peptide previously characterized in the M2GlyR family. Additionally, peptides of the invention have been shown to increase transepithelial electrical conductance and modulate the permeability of tight junctions in epithelial cells.

Claims

12 · 1 independent · depth 2

12 granted claims

›1.independentAn isolated synthetic peptide having a total of from about 16-31 amino acid residues and comprising a plurality of polar amino acid residues at either…+11

›2.↳ 1The peptide of claim 1, said plurality of polar amino acid residues including at least one lysine residue.d2

›3.↳ 1The peptide of claim 1, said plurality of polar amino acid residues comprising up to four lysine residues.d2

›4.↳ 1The peptide of claim 1, said peptide having from about 22-27 amino acid residues.d2

›5.↳ 1The peptide of claim 1, said peptide being substantially monomeric in solution.d2

›6.↳ 1The peptide of claim 1, said peptide being soluble to a level of at least about maybe 1 mM.d2

›7.↳ 1The peptide of claim 1, said peptide being soluble to a level of at least about 10 mM.d2

›8.↳ 1The peptide of claim 1, said peptide having at least about 35% helical content.d2

›9.↳ 1The peptide of claim 1, said peptide having an activity profile of greater than about 15.0 μA/cm2 in MDCK cells when applied to the MDCK cells at a co…d2

›10.↳ 1The peptide of claim 1, said peptide including at least one amino acid residue positioned between said modules.d2

›11.↳ 1The peptide of claim 1, said at least one amino acid residue positioned between said modules being selected from the group consisting of alanine, lysi…d2

›12.↳ 1The isolated synthetic peptide of claim 1, said peptide being selected from the group consisting of SEQ ID Nos. 27, 26, 19, 18, 28, 9, 13, 4, 32, and …d2

Classifications

3 codes

IPC · International Patent Classification

Section C — Chemistry; metallurgy

C07K14/00

USPC · US Patent Classification

530/300530/350

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Pendency

6.4 y

2,339 days filing → grant

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1 RCE

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Examiner

Michael Pak

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Priority chain

2 priority documents

Priority

7 May 2004

earliest claimed

›Priority documents — 2

Type	Document	Date
provisional	US 60569299 00	7 May 2004
related publication	US 20070298494 A1	27 Dec 2007

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