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Ghetie V, Till MA, Ghetie MA, et al. Preparation and characterization of conjugates of recombinant CD4 and deglycosylated ricin A chain using different cross-linkers. Bioconjug Chem. 1990;1(1):24-31doi: 10.1021/bc00001a003.
Ghetie, V., Till, M. A., Ghetie, M. A., Tucker, T., Porter, J., Patzer, E. J., Richardson, J. A., Uhr, J. W., & Vitetta, E. S. (1990). Preparation and characterization of conjugates of recombinant CD4 and deglycosylated ricin A chain using different cross-linkers. Bioconjugate chemistry, 1(1), 24-31. https://doi.org/10.1021/bc00001a003
Ghetie, V, et al. "Preparation and characterization of conjugates of recombinant CD4 and deglycosylated ricin A chain using different cross-linkers." Bioconjugate chemistry vol. 1,1 (1990): 24-31. doi: https://doi.org/10.1021/bc00001a003
Ghetie V, Till MA, Ghetie MA, Tucker T, Porter J, Patzer EJ, Richardson JA, Uhr JW, Vitetta ES. Preparation and characterization of conjugates of recombinant CD4 and deglycosylated ricin A chain using different cross-linkers. Bioconjug Chem. 1990 Jan-Feb;1(1):24-31. doi: 10.1021/bc00001a003. PMID: 2095203.
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Bioconjug Chem. 1990 Jan-Feb;1(1):24-31. doi: 10.1021/bc00001a003.

Preparation and characterization of conjugates of recombinant CD4 and deglycosylated ricin A chain using different cross-linkers.

Bioconjugate chemistry

V Ghetie, M A Till, M A Ghetie, T Tucker, J Porter, E J Patzer, J A Richardson, J W Uhr, E S Vitetta

Affiliations

  1. Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.

PMID: 2095203 DOI: 10.1021/bc00001a003

Abstract

In a previous study, we have demonstrated that conjugates containing soluble, recombinant human CD4 (rCD4) and the deglycosylated form of ricin A chain (dgA) (rCD4-dgA) effectively kill a human T cell line infected with the human immunodeficiency virus (HIV) in vitro. In contrast, such conjugates are 100-1000-fold less toxic to uninfected cells. In order to use a rCD4-dgA conjugate effectively in vivo, it was important to demonstrate that (1) it binds to and kills HIV-infected, but not uninfected, human cells, (2) it is stable in the circulation, and (3) it has an optimal therapeutic index (toxicity to animals versus toxicity to target cells). A major factor affecting the efficacy of such conjugates in vitro and in vivo is the nature of the cross-linker between the ligand (rCD4) and the toxin (dgA). In this report, we have prepared rCD4-dgA conjugates using three different cross-linkers. Different methods of purification have been compared by determining the optimal yield, purity, and retention of biological activity (i.e., binding to gp120 and dgA chain activity). The structure of these conjugates as well as their cytotoxicity to target cells in vitro has been analyzed. Finally, we have compared their pharmacokinetics, tissue localization, and toxicity in mice.

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