Osteotropic Peptide That Differentiates Functional Domains of the Skeleton

• Published in: Bioconjugate chemistry Vol. 18; no. 5; pp. 1375 - 1378
• Main Authors: Wang, Dong, Miller, Scott C, Shlyakhtenko, Luda S, Portillo, Alexander M, Liu, Xin-Ming, Papangkorn, Kongnara, Kopečková, Pavla, Lyubchenko, Yuri, Higuchi, William I, Kopeček, Jindřich
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.09.2007
• Subjects: Alendronate - pharmacology; Animals; Aspartic Acid - analogs & derivatives; Aspartic Acid - pharmacology; Binding Sites; Bone and Bones - pathology; Bone Density Conservation Agents - pharmacology; Bone Resorption - pathology; Diphosphonates - pharmacology; Disease Models, Animal; Drug Delivery Systems - methods; Durapatite - metabolism; Female; Fluorescein-5-isothiocyanate - chemistry; Microscopy; Microscopy, Atomic Force; Oligopeptides - pharmacology; Osteoporosis; Osteoporosis - pathology; Ovariectomy; Peptides; Rats; Rodents; Skeleton; Staining and Labeling; Tissues
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/bc7002132

HPMA copolymer−d-aspartic acid octapeptide (D-Asp8) conjugates have been found to target the entire skeleton after systemic administration. In a recent study using the ovariectomized rat model of osteoporosis, we surprisingly discovered that D-Asp8 would favorably recognize resorption sites in skeletal tissues, while another bone-targeting moiety, alendronate (ALN), directs the delivery system to both formation and resorption sites. Atomic force microscopy (AFM) analyses reveal that ALN has a stronger binding force to hydroxyapatite (HA) than D-Asp8. In vitro HA binding studies indicate that D-Asp8 is more sensitive to change of HA crystallinity than ALN. Because the bone apatite in the newly formed bone (formation sites) usually has lower crystallinity than the resorption sites (mainly mature bone), we believe that the favorable recognition of D-Asp8 to the bone resorption sites could be attributed to its relatively weak binding to apatite, when compared to bisphosphonates, and the different levels of crystallinity of bone apatite at different functional domains of the skeleton.