Reagents and methods for treating dental disease

1. An isolated amelogenin-derived polypeptide consisting of the amino acid sequence of SEQ ID NO:2(PGYIN(L/F)SY(E/A)(K/N/A)SHSQAIN(T/V)(D/A)(R/A)TA) 1-10 (ADP5).

2. The isolated amelogenin-derived polypeptide of claim 1 , wherein the polypeptide is selected from the group consisting of:

(ADP5)

(SEQ ID NO: 24)

(PGYIN( L / F )SYE( K / N )SHSQAIN( T / V )DRTA) 1-10 ;

(ADP5H)

(SEQ ID NO: 6)

(PGYIN F SYE N SHSQAIN V DRTA) 1-10 ;

(ADP5M)

(SEQ ID NO: 7)

(PGYIN L SYE K SHSQAIN T DRTA) 1-10 ;

ADP5(V1):

(SEQ ID NO: 25)

(PGYIN(L/F)SYA(K/N)SHSQAIN(T/V)ARTA) 1-10 ;

ADP5(V2):

(SEQ ID NO: 26)

(PGYIN(L/F)SYE(A/N)SHSQAIN(T/V)DATA) 1-10 ;

ADP5(V3):

(SEQ ID NO: 27)

(PGYIN(L/F)SYA(A/N)SHSQAIN(T/V)AATA) 1-10 ;

(SEQ ID NO: 32)

(PGYINLSYA(K/N)SHSQAINTARTA 1-10 ;

(SEQ ID NO: 33)

(PGYINLSYE(A/N)SHSQAINTDATA) 1-10 ;

(SEQ ID NO: 34)

(PGYINLSYA(A/N)SHSQAINTAATA 1-10 ;

(SEQ ID NO: 35)

(PGYINFSYA(K/N)SHSQAINVARTA) 1-10 ;

(SEQ ID NO: 36)

(PGYINFSYE(A/N)SHSQAINVDATA) 1-10 ;

(SEQ ID NO: 37)

(PGYINFSYA(A/N)SHSQAINVAATA) 1-10 ;

(SEQ ID NO: 38)

(PGYINLSYAKSHSQAINTARTA) 1-10 ;

(SEQ ID NO: 39)

(PGYINLSYEASHSQAINTDATA) 1-10 ;

(SEQ ID NO: 40)

(PGYINLSYAASHSQAINTAATA) 1-10 ;

(SEQ ID NO: 41)

(PGYINFSYANSHSQAINVARTA) 1-10 ;

(SEQ ID NO: 42)

(PGYINFSYEASHSQAINVDATA) 1-10 ;

and

(SEQ ID NO: 43)

(PGYINFSYAASHSQAINVAATA) 1-10 .

3. The isolated amelogenin-derived polypeptide of claim 1 , wherein the polypeptide consists of the amino acid sequence (PGYINFSYENSHSQAINVDRTA) 1-10 (SEQ ID NO: 6) (ADP5H).

4. A recombinant fusion polypeptide, comprising:

(a) the amelogenin-derived polypeptide of claim 1 ; and

(b) a heterologous polypeptide.

5. The recombinant fusion protein of claim 4 , wherein the heterologous polypeptide is selected from the group consisting of detectable polypeptides, polypeptide affinity tags, peptide markers, anti-microbial polypeptides, biomineralization-promoting polypeptides, inorganic material-binding polypeptides, three-dimensional scaffold-forming polypeptides, collagen, chitosan, amphiphilic peptides, protein-binding polypeptides, enamelin-derived polypeptides, tuftelin-derived peptides, statherin-derived polypeptides, dentin-derived polypeptides, bone sialoprotein-derived polypeptides, osteocalcin-derived polypeptides, osteopontin-derived polypeptides, proteins with caries inhibitory activity, casein, and bone morphogenetic-derived polypeptides.

6. A composition, comprising:

(a) the amelogenin-derived polypeptide of claim 1 ; and

(b) a non-peptide moiety linked to the amelogenin-derived polypeptide.

7. The composition of claim 6 , wherein the non-peptide moiety is selected from the group consisting of radioactive isotopes, non-peptide affinity tags, isotope-coded affinity tags, fluorophores, nanotubes, nanowires, nanoparticles, atomic clusters, quantum dots, single layer or multilayer atomic materials, inorganic ions or ion clusters, organic-inorganic hybrid nanostructures, fish flour, amino acids, and non-peptide polymers.

8. A pharmaceutical composition, comprising

(a) the polypeptide of claim 1 ; and

(b) a pharmaceutically acceptable carrier.

9. An oral care product, comprising the polypeptide of claim 1 .

10. The oral care product of claim 9 , wherein the dental care product is selected from the group consisting of toothpaste, toothpowders, mouthwash, dental floss, liquid dentifrices, dental tablets, topical gels, troches, chewing gums, dental pastes, gingival massage creams, gargle tablets, lozenges, and food products.

11. The isolated amelogenin-derived polypeptide of claim 1 , wherein the polypeptide is (PGYINLSYEKSHSQAINTDRTA) 1-10 (SEQ ID NO: 7).

12. A method for treating dental disease, comprising administering to a subject in need thereof an amount effective to treat the dental disease of the polypeptide of claim 1 .

13. The method of claim 12 , wherein the dental disorder is selected from the group consisting of periodontitis, tooth erosion, hypersensitivity, bacterial plaque, dental fluorosis, tooth decay, carries, tooth resorption, and gingival recession.

14. An isolated polypeptide, comprising one or more amino acid sequences selected from the group consisting of:

ADP5(V1):

(SEQ ID NO: 25)

(PGYIN(L/F)SYA(K/N)SHSQAIN(T/V)ARTA) 1-10 ;

ADP5(V2):

(SEQ ID NO: 26)

(PGYIN(L/F)SYE(A/N)SHSQAIN(T/V)DATA) 1-10 ;

and

ADP5(V3):

(SEQ ID NO: 27)

(PGYIN(L/F)SYA(A/N)SHSQAIN(T/V)AATA) 1-10 .

15. The isolated polypeptide of claim 14 , comprising one or more amino acid sequences selected from the group consisting of

ADP5(V1):

(SEQ ID NO: 25)

PGYIN(L/F)SYA(K/N)SHSQAIN(T/V)ARTA;

ADP5(V2):

(SEQ ID NO: 26)

PGYIN(L/F)SYE(A/N)SHSQAIN(T/V)DATA;

ADP5(V3):

(SEQ ID NO: 27)

PGYIN(L/F)SYA(A/N)SHSQAIN(T/V)AATA);

(SEQ ID NO: 32)

PGYINLSYA(K/N)SHSQAINTARTA;

(SEQ ID NO: 33)

PGYINLSYE(A/N)SHSQAINTDATA;

(SEQ ID NO: 34)

PGYINLSYA(A/N)SHSQAINTAATA;

(SEQ ID NO: 35)

PGYINFSYA(K/N)SHSQAINVARTA;

(SEQ ID NO: 36)

PGYINFSYE(A/N)SHSQAINVDATA;

(SEQ ID NO: 37)

PGYINFSYA(A/N)SHSQAINVAATA;

(SEQ ID NO: 38)

PGYINLSYAKSHSQAINTARTA;

(SEQ ID NO: 39)

PGYINLSYEASHSQAINTDATA;

(SEQ ID NO: 40)

PGYINLSYEASHSQAINTDATA;

(SEQ ID NO: 41)

PGYINFSYANSHSQAINVARTA;

(SEQ ID NO: 42)

PGYINFSYEASHSQAINVDATA;

and

(SEQ ID NO: 43)

PGYINFSYAASHSQAINVAATA.

16. A recombinant fusion polypeptide, comprising:

(a) the isolated polypeptide of claim 14 ; and

(b) a heterologous polypeptide.

17. A composition, comprising:

(a) the isolated polypeptide of claim 14 ; and

(b) a non-peptide moiety linked to the polypeptide.

18. A pharmaceutical composition, comprising

(a) the polypeptide of claim 14 ; and

(b) a pharmaceutically acceptable carrier.

19. An oral care product, comprising the polypeptide of claim 14 .

20. The oral care product of claim 19 , wherein the dental care product is selected from the group consisting of toothpaste, toothpowders, mouthwash, dental floss, liquid dentifrices, dental tablets, topical gels, troches, chewing gums, dental pastes, gingival massage creams, gargle tablets, lozenges, and food products.

21. A method for treating dental disease, comprising administering to a subject in need thereof an amount effective to treat the dental disease of the polypeptide of claim 14 .

22. The method of claim 21 , wherein the dental disorder is selected from the group consisting of periodontitis, tooth erosion, hypersensitivity, bacterial plaque, dental fluorosis, tooth decay, carries, tooth resorption, craniomaxillofacial bone disease, and gingival recession.

23. An isolated amelogenin-derived polypeptide comprising the amino acid sequence of SEQ ID NO:2 (PGYIN(L/F)SY(E/A)(K/N/A)SHSQAIN(T/V)(D/A)(R/A)TA) 2-10 .

24. The isolated amelogenin-derived polypeptide of claim 23 , wherein the polypeptide comprises a polypeptide selected from the group consisting of:

(ADP5)

(SEQ ID NO: 24)

(PGYIN( L / F )SYE( K / N )SHSQAIN( T / V )DRTA) 2-10 ;

(ADP5H)

(SEQ ID NO: 6)

(PGYIN F SYE N SHSQAIN V DRTA) 2-10 ;

(ADP5M)

(SEQ ID NO: 7)

(PGYIN L SYE K SHSQAIN T DRTA) 2-10 ;

ADP5(V1):

(SEQ ID NO: 25)

(PGYIN(L/F)SYA(K/N)SHSQAIN(T/V)ARTA) 2-10 ;

ADP5(V2):

(SEQ ID NO: 26)

(PGYIN(L/F)SYE(A/N)SHSQAIN(T/V)DATA) 2-10 ;

ADP5(V3):

(SEQ ID NO: 27)

(PGYIN(L/F)SYA(A/N)SHSQAIN(T/V)AATA) 2-10 ;

(SEQ ID NO: 32)

(PGYINLSYA(K/N)SHSQAINTARTA 2-10 ;

(SEQ ID NO: 33)

(PGYINLSYE(A/N)SHSQAINTDATA) 2-10 ;

(SEQ ID NO: 34)

(PGYINLSYA(A/N)SHSQAINTAATA 2-10 ;

(SEQ ID NO: 35)

(PGYINFSYA(K/N)SHSQAINVARTA) 2-10 ;

(SEQ ID NO: 36)

(PGYINFSYE(A/N)SHSQAINVDATA) 2-10 ;

(SEQ ID NO: 37)

(PGYINFSYA(A/N)SHSQAINVAATA) 2-10 ;

(SEQ ID NO: 38)

(PGYINLSYAKSHSQAINTARTA) 2-10 ;

(SEQ ID NO: 39)

(PGYINLSYEASHSQAINTDATA) 2-10 ;

(SEQ ID NO: 40)

(PGYINLSYAASHSQAINTAATA) 2-10 ;

(SEQ ID NO: 41)

(PGYINFSYANSHSQAINVARTA) 2-10 ;

(SEQ ID NO: 42)

(PGYINFSYEASHSQAINVDATA) 2-10 ;

and

(SEQ ID NO: 43)

(PGYINFSYAASHSQAINVAATA) 2-10 .

25. The isolated amelogenin-derived polypeptide of claim 23 , wherein the polypeptide comprises (PGYINLSYEKSHSQAINTDRTA) 2-10 (SEQ ID NO: 7).

26. A recombinant fusion polypeptide, comprising:

(a) the amelogenin-derived polypeptide of claim 23 ; and

(b) a heterologous polypeptide.

27. The recombinant fusion protein of claim 26 , wherein the heterologous polypeptide is selected from the group consisting of detectable polypeptides, polypeptide affinity tags, peptide markers, anti-microbial polypeptides, biomineralization-promoting polypeptides, inorganic material-binding polypeptides, three-dimensional scaffold-forming polypeptides, collagen, chitosan, amphiphilic peptides, protein-binding polypeptides, enamelin-derived polypeptides, tuftelin-derived peptides, statherin-derived polypeptides, dentin-derived polypeptides, bone sialoprotein-derived polypeptides, osteocalcin-derived polypeptides, osteopontin-derived polypeptides, proteins with caries inhibitory activity, casein, and bone morphogenetic-derived polypeptides.

28. A composition, comprising:

(a) the amelogenin-derived polypeptide of claim 23 ; and

(b) a non-peptide moiety linked to the amelogenin-derived polypeptide.

29. The composition of claim 28 , wherein the non-peptide moiety is selected from the group consisting of radioactive isotopes, non-peptide affinity tags, isotope-coded affinity tags, fluorophores, nanotubes, nanowires, nanoparticles, atomic clusters, quantum dots, single layer or multilayer atomic materials, inorganic ions or ion clusters, organic-inorganic hybrid nanostructures, fish flour, amino acids, and non-peptide polymers.

30. A pharmaceutical composition, comprising

(a) the polypeptide of claim 23 ; and

(b) a pharmaceutically acceptable carrier.

31. An oral care product, comprising the polypeptide of claim 23 .

32. The oral care product of claim 31 , wherein the dental care product is selected from the group consisting of toothpaste, toothpowders, mouthwash, dental floss, liquid dentifrices, dental tablets, topical gels, troches, chewing gums, dental pastes, gingival massage creams, gargle tablets, lozenges, and food products.

33. The isolated amelogenin-derived polypeptide of claim 23 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO:2 (PGYIN(L/F)SY(E/A)(K/N/A)SHSQAIN(T/V)(D/A)(R/A)TA) 2-10 .