Valency-Dependent Affinity of Bioactive Hydroxyapatite-Binding Dendrons

Abstract

Hydroxyapatite (HA)-coated surfaces are used widely as stationary phase for protein and enzyme purification, coatings for dental and orthopedic implants, and composite materials for tissue engineering substrates. More advanced applications are envisioned, but progress has been slowed by the limited ability to controllably functionalize the surface of HA with biomolecules in a translationally relevant manner. Herein we report the synthesis and characterization of a series of multivalent, HA-binding peptide bioconjugates with variable valency and tether length which afford the ability to precisely tune the desired binding behavior. The respective binding affinities of the multivalent constructs to HA surface were characterized by quartz crystal microbalance with dissipation monitoring (QCM-D) techniques, and the relationship between dendron structure and binding affinity was revealed. Tetravalent constructs of HA-binding peptides show a 100-fold enhancement in binding affinity compared to HA-binding peptide sequences reported previously. Both biotin and bone morphogenic protein-2 (BMP-2) derivative peptide were successfully linked to the focal point as initial demonstrations.

“Click” reactions: a versatile toolbox for the synthesis of peptide-conjugates

“…The only limitation is that the desired functional groups must be compatible with the reaction conditions for peptide coupling, deprotection and cleavage; otherwise, certain protection of the functional groups is required. Azide, 29 alkyne, 36 alkene, 37 thiol, 38 maleimide, 39 and aminooxy 40 have successfully been introduced into peptides through this strategy.…”

“…This is the most strong binding motif to HA surface that has been reported, which is significantly useful in drugs for bone healing. 36 Not only have dendrons with a single type of peptide functionality been constructed, but heterofunctionalized dendrons, such as molecule 4, have also been successfully synthesized. As a modular peptide, molecule 4 was developed as a mimic of osteocalcin, containing a hydroxyapatite-binding domain, the peptidefunctionalized dendron, and a cell interacting domain by way Fig.…”

“…4: dendrimeric peptide conjugates containing a BMP-2 peptide (20-mer) and two HA-binding peptides (15-mer). Reprinted from Tang et al 36 with permission from the American Chemical Society. Copyright (2013).…”

“…5: tetrameric HA-binding peptide-functionalized dendron. Reprinted from Tang et al 36 with permission from the American Chemical Society. Copyright (2013).…”

Recent developments and applications of bioinspired dendritic polymers

“…This structure was validated to have a strong binding ability to the HAP surface, especially the tetravalent constructs of (HA) 4 -2 dendron, whose binding affinity to HAP was enhanced 100-fold as compared with a HAP-binding peptide. 80 During the enamel formation process, amelogenin protein proceeds in a stepwise and controlled manner for the oriented growth of apatite crystals. It has a strong tendency to assemble into nanospheres and microribbon structures, which play a crucial role for natural biomineralization.…”