DPP IV, otherwise
known as CD26 lymphocyte T surface
antigen, is
a transmembrane glycoprotein also found in circulation in the blood.
It plays an important role in several processes like glucose metabolism
and T-cell stimulation. Moreover, it is overexpressed in renal, colon,
prostate, and thyroid human carcinoma tissues. It can also serve as
a diagnostic in patients with lysosomal storage diseases. The biological
and clinical importance of having readouts for the activity of this
enzyme, in physiological and disease conditions, has led us to design
a near-infrared (NIR) fluorimetric probe that also has the characteristics
of being ratiometric and excitable by two simultaneous NIR photons.
The probe consists of assembling an enzyme recognition group (Gly-Pro)
(Mentlein, 1999; Klemann et al., 2016) on the two-photon (TP) fluorophore
(derivative of dicyanomethylene-4H-pyran, DCM-NH2) disturbing its NIR characteristic internal charge transfer
(ICT) emission spectrum. When the dipeptide group is released by the
DPP IV-specific enzymatic action, the donor–acceptor DCM-NH2 is restored, forming a system that shows high ratiometric
fluorescence output. With this new probe, we have been able to detect,
quickly and efficiently, the enzymatic activity of DPP IV in living
cells, human tissues, and whole organisms, using zebrafish. In addition,
due to the possibility of being excited by two photons, we can avoid
the autofluorescence and subsequent photobleaching that the raw plasma
has when it is excited by visible light, achieving detection of the
activity of DPP IV in that medium without interference.
The four cyclopropyl stereoisomers of Δ7-dafachronic acids were prepared from the bile acid hyodeoxycholic acid and employed as chemical tools to exploit the importance of the orientation and spatial disposition...
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