Substantially pure zonulin, a physiological modulator of mammalian tight junctions
AssigneeUniversity of Maryland, Baltimore
InventorAlessio Fasano
Life of this patent
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Abstract
A substantially pure mammalian protein, hereinafter "zonulin", that is a physiological modulator of mammalian tight junctions is disclosed, as well as methods for the use of the same.
Claims65
Substantially pure zonulin having an apparent molecular weight of about 47 kDa, as determined by SDS-polyacrylamide gel electrophoresis, which is recognized by both anti-tau polyclonal antibody and by anti-ZOT polyclonal antibody, and is capable of reversibly opening mammalian tight junctions, and wherein said zonulin has an N-terminal amino acid sequence selected from the group consisting of:
- (1) Asn Gln Arg Pro Pro Pro Ala Gly Val Thr Ala Tyr Asp Tyr Leu Val Ile Gln (SEQ ID NO:1);
- (2) Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu (SEQ ID NO:2);
- (3) Val Thr Phe Tyr Thr Asp Ala Val Ser (SEQ ID NO:3);
- (4) Met Leu Gln Lys Ala Glu Ser Gly Gly Val Leu Val Gln Pro Gly Xaa Ser Asn Arg Leu (SEQ ID NO:4);
- and
- (5) Glu Val Gln Leu Val Glu Ser Gly Gly Xaa Leu (SEQ ID NO:7).
A pharmaceutical composition for delivery of a therapeutic agent to the intestine comprising:
- (A) a therapeutic agent;
- and
- (B) an intestinal absorption enhancing effective amount of purified zonulin, wherein said zonulin has an apparent molecular weight of about 47 kDa, as determined by SDS-polyacrylamide gel electrophoresis, which is recognized by both anti-tau polyclonal antibody and by anti-ZOT polyclonal antibody, and is capable of reversibly opening mammalian tight junctions, and wherein said zonulin has an N-terminal amino acid sequence selected from the group consisting of:
- (1) Asn Gln Arg Pro Pro Pro Ala Gly Val Thr Ala Tyr Asp Tyr Leu Val Ile Gln (SEQ ID NO:1);
- (2) Glu Val Gln Leu Val Glu Ser Gly Gly Xaa Leu (SEQ ID NO:7);
- and
- (3) Met Leu Gln Lys Ala Glu Ser Gly Gly Val Leu Val Gln Pro Gly Xaa Ser Asn Arg Leu (SEQ ID NO:4).
A pharmaceutical composition for delivery of a therapeutic agent to the heart comprising:
- (A) a therapeutic agent;
- and
- (B) a heart absorption enhancing effective amount of purified zonulin, wherein said zonulin has an apparent molecular weight of about 47 kDa, as determined by SDS-polyacrylamide gel electrophoresis, which is recognized by both anti-tau polyclonal antibody and by anti-ZOT polyclonal antibody, and is capable of reversibly opening mammalian tight junctions, and wherein said zonulin has an N-terminal amino acid sequence Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu (SEQ ID NO:2).
A pharmaceutical composition for delivery of a therapeutic agent to the brain comprising:
- (A) a therapeutic agent;
- and
- (B) a brain absorption enhancing effective amount of purified zonulin, wherein said zonulin has an apparent molecular weight of about 47 kDa, as determined by SDS-polyacrylamide gel electrophoresis, which is recognized by both anti-tau polyclonal antibody and by anti-ZOT polyclonal antibody, and is capable of reversibly opening mammalian tight junctions, and wherein said zonulin has an N-terminal amino acid sequence Val Thr Phe Tyr Thr Asp Ala Val Ser (SEQ ID NO:3).
A method for delivery of a therapeutic agent comprising administering, to a subject in need thereof, a pharmaceutical composition comprising:
- (A) a therapeutic agent;
- and
- (B) an intestinal absorption enhancing effective amount of purified zonulin, wherein said zonulin has an apparent molecular weight of about 47 kDa, as determined by SDS-polyacrylamide gel electrophoresis, which is recognized by both anti-tau polyclonal antibody and by anti-ZOT polyclonal antibody, and is capable of reversibly opening mammalian tight junctions, and wherein said zonulin has an N-terminal amino acid sequence selected from the group consisting of
- (1) Asn Gln Arg Pro Pro Pro Ala Gly Val Thr Ala Tyr Asp Tyr Leu Val Ile Gln (SEQ ID NO:1);
- (2) Glu Val Gln Leu Val Glu Ser Gly Gly Xaa Leu (SEQ ID NO:7);
- and
- (3) Met Leu Gln Lys Ala Glu Ser Gly Gly Val Leu Val Gln Pro Gly Xaa Ser Asn Arg Leu (SEQ ID NO:4).
A method for delivery of a therapeutic agent comprising administering, to a subject in need thereof, a pharmaceutical composition comprising:
- (A) a therapeutic agent;
- and
- (B) a heart absorption enhancing effective amount of purified zonulin, wherein said zonulin has an apparent molecular weight of about 47 kDa, as determined by SDS-polyacrylamide gel electrophoresis, which is recognized by both anti-tau polyclonal antibody and by anti-ZOT polyclonal antibody, and is capable of reversibly opening mammalian tight junctions, and wherein said zonulin has an N-terminal amino acid sequence Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu (SEQ ID NO:2).
A method for delivery of a therapeutic agent comprising administering, to a subject in need thereof, a pharmaceutical composition comprising:
- (A) a therapeutic agent;
- and
- (B) a brain absorption enhancing effective amount of purified zonulin, wherein said zonulin has an apparent molecular weight of about 47 kDa, as determined by SDS-polyacrylamide gel electrophoresis, which is recognized by both anti-tau polyclonal antibody and by anti-ZOT polyclonal antibody, and is capable of reversibly opening mammalian tight junctions, and wherein said zonulin has an N-terminal amino acid sequence Val Thr Phe Tyr Thr Asp Ala Val Ser (SEQ ID NO:3).
Dependencies are inferred from the claim text.