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Highly Stable, Fluorescence‐Labeled Heptapeptides Substituted with a D‐Amino Acid for the Specific Detection of Oxidized Low‐Density Lipoprotein in Plasma
Author(s) -
Sato Akira,
Yamanaka Hikaru,
Oe Keitaro,
Yokoyama Izumi,
Yamazaki Yoji,
Ebina Keiichi
Publication year - 2015
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12399
Subject(s) - fluorescein isothiocyanate , chemistry , fluorescence , linker , isothiocyanate , amino acid , in vitro , in vivo , biochemistry , lipoprotein , fluorescein , microbiology and biotechnology , cholesterol , biology , physics , quantum mechanics , computer science , operating system
Probes that can detect oxidized low‐density lipoprotein (ox‐ LDL ) in plasma and in atherosclerotic plaques can be useful for the diagnosis, prevention, and treatment of atherosclerosis. Recently, we have reported that two heptapeptides (Lys‐Trp‐Tyr‐Lys‐Asp‐Gly‐Asp, KP6) coupled to fluorescein isothiocyanate ( FITC ) through the ε ‐amino group of N‐terminus Lys in the absence/presence of 6‐amino‐n‐caproic acid ( AC ) linker to FITC —( FITC ) KP 6 and ( FITC ‐ AC ) KP 6—can be useful as fluorescent probes for the specific detection of ox‐ LDL . In this study, to develop the fluorescent peptides with high plasma stability for the specific detection of ox‐ LDL , we investigated the interaction of ( FITC ) KP 6 and ( FITC ‐ AC ) KP 6 substituted with D ‐Lys at the N‐terminus—( FITC )d KP 6 and ( FITC ‐ AC )d KP 6—with ox‐ LDL , and the in vitro stability of these peptides in mouse plasma. ( FITC ) dKP 6 and ( FITC ‐ AC ) dKP 6 bound with high specificity to ox‐ LDL in a dose‐dependent manner, and also to ox‐ LDL in the mouse plasma. Furthermore, ( FITC ) dKP 6 was more stable than ( FITC ) KP 6 in mouse plasma (102.1% versus 69.0% remained after 1 h). These findings strongly suggest that ( FITC ) dKP 6 and ( FITC ‐ AC ) dKP 6 may be effective fluorescent probes with higher plasma stability than ( FITC ) KP 6 and ( FITC ‐ AC ) KP 6 for the specific detection of ox‐ LDL .