Osteoarthritis (OA) or rheumatoid arthritis (RA) require early diagnosis because destruction of cartilage tissue continues and advances these diseases. Since X-ray apparatus are placed in many medical facilities, high sensitive cartilage X-ray probes are thought to be useful and valuable. And these probes are useful for not only diagnostic product but also evaluation in animal experiments for drug discovery. So far, we found that arginine oligomers can act as cartilage selective probes. Comparing binding abilities to cartilage by arginine oligomeric numbers with 4, 8, 12, and 16, the octamer (R8) was found to be most suitable as a cartilage probe. However, for the application of R8 to X-ray cartilage probes, since R8 has high-molecular-weight character (molecular weight without signaling moieties such as fluorescent group is more than 1200), the imaging ability by a signaling moiety per weight is expected to be low. Thus, we aimed to create less low-molecular-weight cartilage probes. R8 was revealed to target mainly chondroitin sulfates widely existing in cartilage tissue by using several cartilage proteoglycan-degrading enzymes. This time, we came up with lysine oligomers connected by their e-amino and a-carboxyl groups. The binding affinity with chondroitin sulfates was assessed using fluorescent polarization and fluorescent imagery with mouse knee joint tissue, suggesting that tetra or more oligomers (the molecular weight without signaling moieties of the pentamer and tetramer are about 530 and 660, respectively) showed more potent binding affinity than less oligomers. In addition, the e-lysine pentamer possessing a triiodobenzene moiety was discovered as a high sensitive cartilage X-ray probe. In this presentation, molecular design, syntheses, and the activities of cartilage probes will be reported.

Structurally simple cartilage probes constructed with e-lysine oligomers targeting chondroitin sulfates

246th National Meeting (2013)

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