Modulation of luminescence intensity of lanthanide complexes by photoinduced electron transfer and its application to a long-lived protease probe.
Luminescent lanthanide complexes (Tb(3+), Eu(3+), etc.) have excellent properties for biological applications, including extraordinarily long lifetimes and large Stokes shifts. However, there have been few reports of lanthanide-based functional probes, because of the difficulty in designing suitable complexes with a luminescent on/off switch. Here, we have synthesized a series of complexes which consist of three moieties: a lanthanide chelate, an antenna, and a luminescence off/on switch. The antenna is an aromatic ring which absorbs light and transmits its energy to the metal, and the switch is a benzene derivative with a different HOMO level. If the HOMO level is higher than a certain threshold, the complex emits no luminescence at all, which indicates that the lanthanide luminescence can be modulated by photoinduced electron transfer (PeT) from the switch to the sensitizer. This approach to control lanthanide luminescence makes possible the rational design of functional lanthanide complexes, in which the luminescence property is altered by a biological reaction. To exemplify the utility of our approach to the design of lanthanide complexes with a switch, we have developed a novel protease probe, which undergoes a significant change in luminescence intensity upon enzymatic cleavage of the substrate peptide. This probe, combined with time-resolved measurements, was confirmed in model experiments to be useful for the screening of inhibitors, as well as for clinical diagnosis.
Terai
Takuya
T
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Kikuchi
Kazuya
K
Iwasawa
Shin-ya
SY
Kawabe
Takao
T
Hirata
Yasunobu
Y
Urano
Yasuteru
Y
Nagano
Tetsuo
T
D002624:Chemistry, Clinical / Q000379:methods; D006801:Humans; D007700:Kinetics; D028581:Lanthanoid Series Elements / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D007931:Leucyl Aminopeptidase / Q000097:blood* / Q000378:metabolism; D049449:Luminescence; D009369:Neoplasms / Q000097:blood / Q000201:enzymology; D010447:Peptide Hydrolases / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D010777:Photochemistry / Q000379:methods*; D011480:Protease Inhibitors / Q000494:pharmacology; D012016:Reference Values; D013329:Structure-Activity Relationship
D028581:Lanthanoid Series Elements; D011480:Protease Inhibitors; D010447:Peptide Hydrolases; D007931:Leucyl Aminopeptidase