An Allysine-Conjugatable Probe for Fluorogenically Imaging Fibrosis

Area of Science:

• Biochemistry
• Medical Imaging
• Organic Chemistry

Background:

• Allysine is a key biomarker in fibrogenesis.
• Existing radioactive imaging probes for allysine are available, but fluorogenic probes are underdeveloped.
• Fluorogenic probes offer advantages in sensitivity and specificity for disease detection.

Purpose of the Study:

• To develop a novel fluorogenic probe for detecting allysine, a biomarker for fibrosis.
• To fine-tune the environmental sensitivity of rhodamine-cyanine hybrid fluorophores for fibrosis imaging.
• To create a probe with superior imaging contrast compared to traditional methods.

Main Methods:

• Leveraged the equilibrium between nonfluorescent spirocyclic and fluorescent zwitterionic forms of rhodamine-cyanine hybrid fluorophores.
• Modulated the nucleophilicity of the ortho-carboxyl group, terminated with a hydrazide for allysine conjugation.
• Developed and tested probe B2, featuring an N-sulfonyl amide group, for its fluorogenic response to allysine.

Main Results:

• Probe B2 exhibited a notable fluorogenic response upon conjugation with protein allysine, transitioning from nonfluorescent aggregates to a fluorescent zwitterionic form.
• Probe B2 demonstrated superior fibrosis-to-control imaging contrast (260-2600-fold increase) compared to Masson staining.
• The probe effectively evaluated the efficacy of antifibrosis drugs in preclinical models.

Conclusions:

• The developed fluorogenic probe B2 shows significant potential as an alternative to conventional fibrosis detection methods.
• Probe B2 offers enhanced imaging contrast and is valuable for antifibrosis drug evaluation.
• This strategy provides a new platform for developing sensitive and specific fluorogenic probes for fibrogenesis biomarkers.