Diener E, Diner U E, Sinha A, Xie S, Vergidis R
Science. 1986 Jan 10;231(4734):148-50. doi: 10.1126/science.3484557.
Daunomycin, when conjugated with a targeting antigen by an acid-sensitive spacer, remains inactive at the intravascular pH of 7 but becomes active after cleavage within the acidic lysosomal environment of the target cell. This observation made it possible to construct cytocidal compounds that caused antigen-specific suppression of murine lymphocyte function. When daunomycin was coupled to the hapten conjugate of ovalbumin by an acid-sensitive cis-aconityl group, it caused hapten-specific impairment of immunocompetence in murine B lymphocytes in vitro and in vivo. Furthermore, the response by T lymphocytes to concanavalin A in vitro was selectively eliminated by a conjugate between daunomycin plus the acid-sensitive spacer and a monoclonal antibody specific for T cells.
柔红霉素通过酸敏感间隔基与靶向抗原偶联后，在血管内pH值为7时仍无活性，但在靶细胞酸性溶酶体环境中裂解后变得有活性。这一发现使得构建能导致抗原特异性抑制小鼠淋巴细胞功能的杀细胞化合物成为可能。当柔红霉素通过酸敏感的顺乌头酰基与卵清蛋白的半抗原结合物偶联时，它在体外和体内均导致小鼠B淋巴细胞免疫活性的半抗原特异性损伤。此外，柔红霉素加酸敏感间隔基与T细胞特异性单克隆抗体之间的结合物在体外选择性消除了T淋巴细胞对刀豆球蛋白A的反应。
