Specific binding and mineralization of calcified surfaces by small peptides.
Several small (<25aa) peptides have been designed based on the sequence of the dentin phosphoprotein, one of the major noncollagenous proteins thought to be involved in the mineralization of the dentin extracellular matrix during tooth development. These peptides, consisting of multiple repeats of the tripeptide aspartate-serine-serine (DSS), bind with high affinity to calcium phosphate compounds and, when immobilized, can recruit calcium phosphate to peptide-derivatized polystyrene beads or to demineralized human dentin surfaces. The affinity of binding to hydroxyapatite surfaces increases with the number of (DSS)(n) repeats, and though similar repeated sequences-(NTT)(n), (DTT)(n), (ETT)(n), (NSS)(n), (ESS)(n), (DAA)(n), (ASS)(n), and (NAA)(n)-also showed HA binding activity, it was generally not at the same level as the natural sequence. Binding of the (DSS)(n) peptides to sectioned human teeth was shown to be tissue-specific, with high levels of binding to the mantle dentin, lower levels of binding to the circumpulpal dentin, and little or no binding to healthy enamel. Phosphorylation of the serines of these peptides was found to affect the avidity, but not the affinity, of binding. The potential utility of these peptides in the detection of carious lesions, the delivery of therapeutic compounds to mineralized tissues, and the modulation of remineralization is discussed.
Yarbrough
Daniel K
DK
School of Dentistry, University of California, Los Angeles, CA 90095-1668, USA.
Hagerman
Elizabeth
E
Eckert
Randal
R
He
Jian
J
Choi
Hyewon
H
Cao
Nga
N
Le
Karen
K
Hedger
Jennifer
J
Qi
Fengxia
F
Anderson
Maxwell
M
Rutherford
Bruce
B
Wu
Ben
B
Tetradis
Sotiris
S
Shi
Wenyuan
W
D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003731:Dental Caries / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology; D003804:Dentin / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D017886:Durapatite / Q000737:chemistry / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D012795:Sialoglycoproteins / Q000737:chemistry* / Q000378:metabolism; D014070:Tooth / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D014074:Tooth Calcification / Q000187:drug effects* / Q000502:physiology; D000099311:Dentin Sialophosphoprotein
D017886:Durapatite; D016326:Extracellular Matrix Proteins; D010455:Peptides; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein