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Stability and cytotoxicity of Fab-ricin A immunotoxins prepared with water soluble long chain heterobifunctional crosslinking agents

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  • Microbiology & Immunology
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Abstract

The effects of the hindered and non-hindered water soluble long-chain disulfide bonds on the stability and cytotoxicity of the ricin A chain (RTA) immunotoxin were examined. The RTA immunotoxins were prepared with the Fab fragments of anti-common acute lymphoblastic leukemia antigen (CALLA) monoclonal antibody (Fab-RTA) using sulfosuccinimidyl-6-[(-methyl-(-(2-pyridyldithio)toluamido] hexanoate (S-LC-SMPT) and sulfosuccinimidyl-6-[3-(2-pyridyldi-thio)-propionamido]hexanoate (S-LC-SPDP). The prepared Fab-RTA immunotoxins were evaluated for their conjugation yield, immunoreactivity, thermal and disulfide bond stability and cytotoxicity. The conjugation yield of the Fab-RTA immunotoxin from the water soluble long chain crosslinking agents, S-LC-SMPT and S-LC-SPDP, were comparable. Both Fab-RTA immunotoxins exhibited a similar immunoreactivity and thermal stability in aqueous solution. However, S-LC-SMPT mediated Fab-RTA, sterically hindered, showed an enhanced disulfide bond stability in vitro over S-LC-SPDP mediated one. In the cytotoxicity against antigenic cell Daudi, the S-LC-SMPT mediated RTA immunotoxin maintained a comparable cytotoxicity, compared with S-LC-SPDP mediated Fab-RTA immunotoxin.

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Authors and Affiliations

  1. College of Pharmacy, SungKyunKwan University, 300 Chonchon-dong, Jangan-ku, 440-746, Suwon City, Korea

    Byung Ho Woo, Jung Tae Lee, Myung Ok Park, Kang Ro Lee, Jeung Whan Han, Eun-Seok Park, Sun Dong Yoo & Kang Choon Lee

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  1. Byung Ho Woo
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  2. Jung Tae Lee
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  3. Myung Ok Park
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  4. Kang Ro Lee
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  7. Sun Dong Yoo
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  8. Kang Choon Lee
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Correspondence to Kang Choon Lee.

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Woo, B.H., Lee, J.T., Park, M.O. et al. Stability and cytotoxicity of Fab-ricin A immunotoxins prepared with water soluble long chain heterobifunctional crosslinking agents. Arch Pharm Res 22, 459–463 (1999). https://doi.org/10.1007/BF02979153

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  • DOI: https://doi.org/10.1007/BF02979153

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