We at 3Helix want to help researchers solve problems in their field and obtain new insights with our CHP products. We are working on commercializing a NEW fluorescently labeled CHP for in vivo use! The new probe will provide highly specific binding to areas of collagen turnover in animal models. This new probe has a unique sequence which interferes with their inherent ability to self-trimerize, making it easy and reliable to use in vivo. This work was done by our own Luke Bennink and Michael Yu while at the University of Utah and was published in Biomaterials. It showcases the ability of the new CHP to resist self-trimerization while maintaining a high affinity for denatured collagen. The paper also shows how signal intensity from CHPs correlates to the severity of bone lesions caused by multiple myeloma.
Abstract: Degradation of the extracellular matrix (ECM) is one of the fundamental factors contributing to a variety of life-threatening or disabling pathological conditions. However, a thorough understanding of the degradation mechanism and development of new ECM-targeting diagnostics are severely hindered by a lack of technologies for direct interrogation of the ECM structures at the molecular level. Previously we demonstrated that the collagen hybridizing peptide [CHP, sequence: (GPO)9, O: hydroxyproline] can specifically recognize the degraded and unfolded collagen chains through triple helix formation. Here we show that fluorescently labeled CHP robustly visualizes the pericellular matrix turnover caused by proteolytic migration of cancer cells within 3D collagen culture, without the use of synthetic fluorogenic matrices or genetically modified cells. To facilitate in vivo imaging, we modified the CHP sequence by replacing each proline with a (2S,4S)-4-fluoroproline (f) residue which interferes with the peptide's inherent propensity to self-assemble into homo-triple helices. We show that the new CHP, (GfO)9, tagged with a near-infrared fluorophore, enables in vivo imaging and semi-quantitative assessment of osteolytic bone lesions in mouse models of multiple myeloma. Compared to conventional techniques (e.g., micro-CT), CHP-based imaging is simple and versatile in vitro and in vivo. Therefore, we envision CHP's applications in broad biomedical contexts ranging from studies of ECM biology and drug efficiency to development of clinical molecular imaging.
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