The structure–activity relationship of various YO compounds, novel plasmin inhibitors, in the apoptosis induction

• Published in: Biochimica et biophysica acta Vol. 1674; no. 3; pp. 291 - 298
• Main Authors: Enomoto, Riyo, Sugahara, Chiyoko, Komai, Tomoe, Suzuki, Chie, Kinoshita, Noriko, Hosoda, Akiko, Yoshikawa, Asa, Tsuda, Yuko, Okada, Yoshio, Lee, Eibai
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2004
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Dipeptides - chemistry; Dipeptides - pharmacology; DNA Fragmentation - drug effects; Fibrinolysin - antagonists & inhibitors; Male; Molecular Conformation; Plasmin inhibitor; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Thymocyte; YO compound; YO-2; YO-2; YO compound; Plasmin inhibitor; Thymocyte; Structure–activity relationship; Apoptosis
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2004.07.004

We have previously reported that YO-2, a selective plasmin inhibitor, induces thymocyte apoptosis. To elucidate the mechanism of YO-2-induced apoptosis, other YO compounds with different plasmin inhibitory action were tested for the pro-apoptotic activity in this study. The treatment of rat thymocytes with the YO compounds which had the hydrophobic but not the hydrophilic moiety at the C-terminal increased DNA fragmentation, the number of condensed nuclei and caspase-3-like activity. All pro-apoptotic YO compounds not only were potent plasmin inhibitors but also had the hydrophobic C-terminal as the common structure. Therefore, the target molecule of the YO compounds may be located not on the cell surface but rather inside the cells.