Novel beta-defensins
OwnerDavid A. Adler, James L. Holloway +3inventors
InventorsDavid A. Adler, James L. Holloway, Nand Baindur, Stephanie Beigel-Orme, Paul O. Sheppard
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Abstract
The present invention relates to polynucleotide and polypeptide molecules for zamp1, a novel member of the β-defensin family. The polypeptides, and polynucleotides encoding them, exhibit anti-microbial activity and may be used in the study or treatment of microbial infections. The present invention also includes antibodies to the zamp1 polypeptides.
Claims155
An isolated protein comprising a polypeptide that is at least 80% identical to a polypeptide selected from the group consisting of:
- a) a polypeptide having the sequence of amino acid residue 1 to amino acid residue 65 of SEQ ID NO:2;
- b) a polypeptide having the sequence of amino acid residue 19 to amino acid residue 65 of SEQ ID NO:2;
- c) a polypeptide having the sequence of amino acid residue 21 to amino acid residue 65 of SEQ ID NO:2;
- d) a polypeptide having the sequence of amino acid residue 1 to amino acid residue 67 of SEQ ID NO:10;
- e) a polypeptide having the sequence of amino acid residue 21 to amino acid residue 67 of SEQ ID NO:10;
- and
- f) a polypeptide having the sequence of amino acid residue 23 to amino acid residue 67. of SEQ ID NO:2;
- wherein said polypeptide has cysteine residues corresponding to amino acid residues 33, 40, 45, 55, 62 and 63 of SEQ ID NO:2 or 10.
A polypeptide selected from the group consisting of:
- a) amino acid residue 30 to amino acid residue 63 of SEQ ID NO:2;
- b) amino acid residue 31 to amino acid residue 63 of SEQ ID NO:2;
- c) amino acid residue 30 to amino acid residue 64 of SEQ ID NO:2;
- d) amino acid residue. 31 to amino acid residue 64 of SEQ ID NO:2;
- and
- e) a polypeptide chosen from SEQ ID NOS:14-72.
An isolated polynucleotide molecule encoding a protein, said polynucleotide molecule consisting of a coding strand and a complementary non-coding strand, wherein said polynucleotide molecule encodes a polypeptide that is at least 80% identical to the amino acid sequence to a polypeptide selected from the group consisting of:
- a) a polypeptide having the sequence of amino acid residue 1 to amino acid residue 65 of SEQ ID NO:2;
- b) a polypeptide having the sequence of amino acid residue 19 to amino acid residue 65 of SEQ ID NO:2;
- c) a polypeptide having the sequence of amino acid residue 21 to amino acid residue 65 of SEQ ID NO:2;
- d) a polypeptide having the sequence of amino acid residue 1 to amino acid residue 67 of SEQ ID NO:10;
- e) a polypeptide having the sequence of amino acid residue 21 to amino acid residue 67 of SEQ ID NO:10;
- and
- f) a polypeptide having the sequence of amino acid residue 23 to amino acid residue 67 of SEQ ID NO:2;
- wherein said polypeptide has cysteine residues corresponding to amino acid residues 33, 40, 45, 55, 62 and 63 of SEQ ID NO:2 or 10.
An isolated polynucleotide molecule encoding a protein having cysteine residues corresponding to amino acid residues 33, 40, 45, 55, 62 and 63 of SEQ ID NO:10, said polynucleotide molecule consisting of a coding strand and a complementary non-coding strand, wherein said polynucleotide comprises a nucleotide sequence that is at least 80% identical to the sequence of a polynucleotide selected from the group consisting of:
- a) a polynucleotide as shown in SEQ ID NO:9 from nucleotide 220 to nucleotide 420;
- b) a polynucleotide as shown in SEQ ID NO:9 from nucleotide 280 to nucleotide 420;
- and
- c) a polynucleotide as shown in SEQ ID NO:9 from nucleotide 286 to nucleotide 420.
An isolated polynucleotide molecule encoding a protein having cysteine residues corresponding to amino acid residues 33, 40, 45, 55, 62 and 63 of SEQ ID NO:10, said polynucleotide molecule consisting of a coding strand and a complementary non-coding strand, wherein said polynucleotide comprises a nucleotide sequence as shown in SEQ ID NO:11.
An isolated polynucleotide molecule encoding a polypeptide selected from the group consisting of:
- a) amino acid residue 30 to amino acid residue 63 of SEQ ID NO:2;
- b) amino acid residue 31 to amino acid residue 63 of SEQ ID NO:2;
- c) amino acid residue 30 to amino acid residue 64 of SEQ ID NO:2;
- d) amino acid residue 31 to amino acid residue 64 of SEQ ID NO:2;
- and
- e) a polypeptide chosen from SEQ ID NO:14-72.
An isolated polynucleotide molecule selected from the group consisting of:
- a) nucleotide 88 to nucleotide 189 of SEQ ID NO:
- 1;
- b) nucleotide 88 to nucleotide 192 of SEQ ID NO:
- 1;
- c) nucleotide 91 to nucleotide 189 of SEQ ID NO:
- 1;
- d) nucleotide 91 to nucleotide 192 of SEQ ID NO:1;
- e) nucleotide 88 to nucleotide 189 of SEQ ID NO:4;
- f) nucleotide 88 to nucleotide 192 of SEQ ID NO:4;
- g) nucleotide 91 to nucleotide 189 of SEQ ID NO:4 and
- h) nucleotide 91 to nucleotide 192 of SEQ ID NO:4.
An oligonucleotide probe or primer comprising at least 14 contiguous nucleotides of a polynucleotide of SEQ ID NO:
- 11 or a sequence complementary to SEQ ID NO:
- 11.
A method of treating a microbial-related disease comprising administering to a mammal a therapeutically effective amount of a polypeptide selected from the group consisting of:
- a) a polypeptide of SEQ ID NO:2;
- b) a polypeptide of SEQ ID NO:10;
- c) a polypeptide chosen from SEQ ID NO:14-72;
- h) amino acid residue 30 to amino acid residue 63 of SEQ ID NO:2;
- i) amino acid residue 31 to amino acid residue 63 of SEQ ID NO:2;
- j) amino acid residue 30 to amino acid residue 64 of SEQ ID NO:2;
- k) amino acid residue 31 to amino acid residue 64 of SEQ ID NO:2;
- l) amino acid residue 20 to amino acid residue 67 of SEQ ID NO:10 and
- m) amino acid residue 22 to amino acid residue 67 of SEQ ID NO:10;
- whereby said polypeptide ameliorates said disease.
A method of claim 23, wherein said microbial-related disease is associated with the eye.
A method of claim 23, wherein said microbial-related disease is associated with the ear.
A method of contraception comprising administering to a mammal a therapeutically effective amount of a polypeptide selected from the group consisting of:
- a) a polypeptide of SEQ ID NO:2;
- b) a polypeptide of SEQ ID NO:10;
- c) a polypeptide chosen from SEQ ID NOS:14-72;
- h) amino acid residue 30 to amino acid residue 63 of SEQ ID NO:2;
- i) amino acid residue 31 to amino acid residue 63 of SEQ ID NO:2;
- j) amino acid residue 30 to amino acid residue 64 of SEQ ID NO:2;
- k) amino acid residue 31 to amino acid residue 64 of SEQ ID NO:2;
- l) amino acid residue 20 to amino acid residue 67 of SEQ ID NO:10 and
- m) amino acid residue 22 to amino acid residue 67 of SEQ ID NO:10.
A pharmaceutical composition for treating a microbial infection in a mammal, the composition comprising:
- a polypeptide comprising a sequence of amino acids selected from the group consisting of:
- a) amino acid residue 1 to amino acid residue 65 of SEQ ID NO:2;
- b) amino acid residue 19 to amino acid residue 65 of SEQ ID NO:2;
- c) amino acid residue 21 to amino acid residue 65 of SEQ ID NO:2;
- d) amino acid residue 30 to amino acid residue o63 f SEQ ID NO:2;
- e) amino acid residue 31 to amino acid residue 63 of SEQ ID NO:2;
- f) amino acid residue 30 to amino acid residue 64 of SEQ ID NO:2;
- g) amino acid residue 31 to amino acid residue 64 of SEQ ID NO:2;
- h) amino acid residue 1 to amino acid residue 67 of SEQ ID NO:10;
- i) amino acid residue 21 to amino acid residue 67 of SEQ ID NO:10;
- j) amino acid residue 23 to amino acid residue 67 of SEQ ID NO:10;
- k) a polypeptide chosen from SEQ ID NOS:14-72;
- and
- l) combinations thereof;
- an antimicrobial agent;
- and
- a pharmaceutically acceptable carrier.
A pharmaceutical composition for treating a microbial infection in a mammal, the composition comprising:
- a polypeptide comprising a sequence of amino acids having at least 95% sequence identity to the sequence of amino acid residues selected from the group consisting of:
- a) amino acid residue 1 to amino acid residue 65 of SEQ ID NO:2;
- b) amino acid residue 19 to amino acid residue 65 of SEQ ID NO:2;
- c) amino acid residue 21 to amino acid residue 65 of SEQ ID NO:2;
- d) amino acid residue 30 to amino acid residue 63 of SEQ ID NO:2;
- e) amino acid residue 31 to amino acid residue 63 of SEQ ID NO:2;
- f) amino acid residue 30 to amino acid residue 64 of SEQ ID NO:2;
- g) amino acid residue 31 to amino acid residue 64 of SEQ ID NO:2;
- h) amino acid residue 1 to amino acid residue 67 of SEQ ID NO:10;
- i) amino acid residue 21 to amino acid residue 67 of SEQ ID NO:10;
- j) amino acid residue 23 to amino acid residue 67 of SEQ ID NO:10;
- k) a polypeptide chosen from SEQ ID NOS:14-72;
- and
- l) combinations thereof;
- an antimicrobial agent;
- and
- a pharmaceutically acceptable carrier;
- wherein the antimicrobial activity of the composition is greater than the antimicrobial activity of the polypeptide and antimicrobial agent alone under similar conditions.
Dependencies are inferred from the claim text.