Selection and identification of a novel bone-targeting peptide for biomedical imaging of bone

Abstract

The global burden of bone-related diseases is increasing in the aging society; thus, improved bone targeted imaging for their early identification and treatment are needed. In this study, we screened novel peptide ligands for hydroxyapatite, a major inorganic component of teeth and bones, and identified a peptide enabling in vivo bone targeting and real-time fluorescence bone detection. To isolate peptides highly specific for hydroxyapatite, we used negative and positive selection from a randomized 8-mer peptide phage library and identified hydroxyapatite-specific peptides (HA-pep2, HA-pep3, and HA-pep7). Among these three peptides, HA-pep3 showed the highest binding capacity and superior dissociation constant towards hydroxyapatite surfaces over time (~ 88.3% retained on hydroxyapatite after two weeks). Furthermore, HA-pep3 was highly specific for hydroxyapatite compared to other calcium salt-based materials. Using this superior specificity, HA-pep3 showed higher accumulation in skull, spine, and joints in comparison with scrambled control peptide during real-time whole-body imaging. Ex vivo analysis of the major organs and bone from mice demonstrated that the fluorescence intensity in bone was about 3.32 folds higher in the case of HA-pep3 than the one exhibited by the scrambled control peptide. Our study identified a novel approach for targeting ligands for bone specific imaging and can be useful for drug delivery applications.

Investigating the Role of Amino Acids in Short Peptides for Hydroxyapatite Binding and Osteogenic Differentiation of Mesenchymal Stem Cells to Aid Bone Regeneration

“…have also discussed the role of noncollagenous proteins enriched with acidic and phosphorylated amino acid in regulating the nucleation and growth of HAp for bone mineralization. Bang et al have compared the HAp binding affinities of a set of peptides with positive (basic amino acids) and negative charge (acidic amino acids) and illustrated that the positively charged peptides (KNFQSRSH) exhibited better binding with HAp . Gungormus et al also reported the ionic interaction of positively charged, histidine-binding peptides with phosphates of HAp .…”

AP-2δ Is the Most Relevant Target of AP-2 Family-Focused Cancer Therapy and Affects Genome Organization

“…As revealed using the fourth Garnier–Osguthorpe–Robson algorithm (GOR4), out of the entire AP-2 family, AP-2δ has the largest number of extended strands but the smallest of random coils ( Figure 2 E). Bang et al suggested that binding affinity could be elevated with the increase of extended strands in secondary structure [ 38 ]. Particular attention was also given to the amino acids preceding the conserved “TF_AP-2” domain; these were evaluated for their similarity, physicochemical properties, and structural characteristics ( Figure 3 ).…”

A sticky tale : Biomaterial coatings from modular proteins

“…In another example, Bang et al identified a supposedly highly specific HA-binding peptide via phage display and combined it with the fluorescent Cy5.5 dye. 180 During in vivo real-time wholebody imaging, the conjugate showed preferential binding for bone tissues. The development of probes for nuclear imaging was also attempted, but with unsatisfactory results.…”