[1][2] A CHP peptide usually possesses a high content of proline and hydroxyproline in the Xaa and Yaa positions, which confers it a strong propensity to form the collagen's unique triple helix conformation.
[2] This occurs via the triple helical chain assembly and inter-chain hydrogen bonding, in a manner similar to primers binding to melted DNA strands during PCR.
[2] Single-stranded CHPs bind to denatured collagen chains and gelatin in a manner that is unique from other targeting mechanisms, in that they specifically recognize a unique structural motif (collagen triple helix) for folding and chain assembly, as opposed to specific epitopes binding that is seen for monoclonal antibodies (mAbs), for example.
[17] CHPs can target tissues undergoing remodelling based on their ability to bind to degraded and unfolded collagen strands through triple helix formation.
As a targeting moiety, CHPs offer great potential in histopathology, diagnostics, and drug delivery for a wide range of diseases.
[14][15] CHP is applicable to tissue specimens from multiple species and a range of diseases, such as myocardial infarction, arthritis, nephritis, and fibrosis.
Schematic of a CHP strand (labeled with an "X" tag) hybridizing to denatured collagen chains and forming a collagen triple helix. During disease progression, tissue development, or ageing, collagen can be extensively degraded by collagenolytic proteases, causing its triple helix to unfold at the physiological temperature due to reduced thermal stability. X may represent a biotin or fluorescent tag.
Schematic showing relationship between the CMP and CHP. Triple helical CMPs can be heated (above a defined temperature) to dissociate into monomeric CHPs; upon cooling, CHP strands can re-assemble into a triple helix over time.
A fluorescence image of an axial cross section of a mouse heart at day 14 post myocardial infarction, stained with Hoechst 33342 (blue) and biotin-labeled CHP (detected with AlexaFluor647-streptavidin, red). Scale bar: 1 mm.
A fluorescence image of a sagittal section of an 18 d.p.c. mouse embryo double stained with biotinylated-CHP (detected by AlexaFluor647-streptavidin, orange) and an anti-collagen I antibody (detected by AlexaFluor555-labeled donkey anti-rabbit IgG H&L, cyan). mx, maxilla; md, mandibular bone; bp, basisphenoid bone; bo, basioccipital bone; vc, vertebral column; rb, rib; h, hipbone; d, digital bones. Scale bar: 3 mm.
