Archives of Pharmacal Research
- Volume 22 Issue 5
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- Pages.459-463
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- 1999
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- 0253-6269(pISSN)
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- 1976-3786(eISSN)
Stability and Cytotoxicity of Fab-Ricin A Immunotoxins Prepared with Water Soluble Long Chain Heterobifunctional Crosslinking Agents
- Woo, Byung-Ho (College of Pharmacy, SungKyunKwan University) ;
- Lee, Jung-Tae (College of Pharmacy, SungKyunKwan University) ;
- Park, Myung-Ok (College of Pharmacy, SungKyunKwan University) ;
- Lee, Kang-Ro (College of Pharmacy, SungKyunKwan University) ;
- Han, Jeung-Whan (College of Pharmacy, SungKyunKwan University) ;
- Park, Eun-Seok (College of Pharmacy, SungKyunKwan University) ;
- Yoo, Sun-Dong (College of Pharmacy, SungKyunKwan University) ;
- Lee, Kang-Choon (College of Pharmacy, SungKyunKwan University)
- Published : 1999.10.01
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]toluamido]hexanoate (S-LC-SMPT) and sulfosuccinimidyl-6-[3-(2-pyridyldithio-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.