Crystallization of intact monoclonal antibodies
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Updated: Nov 6, 2026

Generation of Murine Monoclonal Antibodies by Hybridoma Technology
Published on: January 2, 2017
L J Harris1, E Skaletsky, A McPherson
1Department of Biochemistry, University of California, Riverside 92521, USA.
Attempts were made to crystallize four monoclonal antibodies, one IgG2a kappa and three IgG1 kappa. Using a PEG 3350 screen combined with detergents, and developed from our experiments with an IgG2a kappa antibody specific for canine lymphoma cells, crystals have now been obtained of two of these four immunoglobulins, an antiphenytoin and an antiphenobarbital antibody. A complex between the antiphenobarbital antibody and its drug antigen crystallized as well. The antibody for phenytoin has, to this point, produced only clustered microcrystals, marginally suitable for X-ray analysis. Single crystals of the IgG1 kappa antibody against phenobarbital, however, were characterized by X-ray diffraction to be primitive monoclinic, with unit cell dimensions a = 67 A, b = 193 A, c = 74 A, and beta = 110 degrees. These crystals have an entire IgG1 kappa molecule as the asymmetric unit and they diffract to at least 3.2 A resolution.
Attempts were made to crystallize four monoclonal antibodies, one IgG2a kappa and three IgG1 kappa. Using a PEG 3350 screen combined with detergents, and developed from our experiments with an IgG2a kappa antibody specific for canine lymphoma cells, crystals have now been obtained of two of these four immunoglobulins, an antiphenytoin and an antiphenobarbital antibody. A complex between the antiphenobarbital antibody and its drug antigen crystallized as well. The antibody for phenytoin has, to this point, produced only clustered microcrystals, marginally suitable for X-ray analysis. Single crystals of the IgG1 kappa antibody against phenobarbital, however, were characterized by X-ray diffraction to be primitive monoclinic, with unit cell dimensions a = 67 A, b = 193 A, c = 74 A, and beta = 110 degrees. These crystals have an entire IgG1 kappa molecule as the asymmetric unit and they diffract to at least 3.2 A resolution.
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