Design of Optical-Imaging Probes by Screening of Diverse Substrate Libraries Directly in Disease-Tissue Extracts.
Angew Chem Int Ed Engl
; 59(43): 19143-19152, 2020 10 19.
Article
in En
| MEDLINE
| ID: mdl-32589815
ABSTRACT
Fluorescently quenched probes that are specifically activated in the cancer microenvironment have great potential application for diagnosis, early detection, and surgical guidance. These probes are often designed to target specific enzymes associated with diseases by direct optimization using single purified enzymes. However, this can result in painstaking chemistry efforts to produce a probe with suboptimal performance when applied inâ
vivo. We describe here an alternate, unbiased activity-profiling approach in which whole tissue extracts are used to directly identify optimal peptide sequences for probe design. Screening of tumor extracts with a hybrid combinatorial substrate library (HyCoSuL) identified a combination of natural and non-natural amino-acid residues that was used to generate highly efficient tumor-specific probes. This new strategy simplifies and enhances the process of probe optimization without any aâ
priori knowledge of enzyme targets and has the potential to be applied to diverse disease states using clinical or animal-model tissue samples.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Optical Imaging
/
Fluorescent Dyes
Type of study:
Diagnostic_studies
/
Guideline
/
Prognostic_studies
/
Screening_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Angew Chem Int Ed Engl
Year:
2020
Type:
Article
Affiliation country:
United States