Abstract：
PURPOSE:To investigate the underlying cause for the observed differences in self-associating and viscoelastic behavior between two monoclonal antibodies, MAb1, and MAb2. METHODS:Several mutants were designed by swapping charged residues in MAb1 with those present in MAb2 at their respective positions and vice versa. Rheological analysis was done at low and high shear rates. Dynamic light scattering quantified intermolecular interactions in dilute solutions; sedimentation equilibrium analysis determined the corrected weight average molecular weight (M (wc)) to assess the self-associating behavior in high concentration. The molecular charge was estimated from electrophoretic mobility measurements. RESULTS:Replacing the charged residues in the CDR of MAb1 resulted in a lower M (wc) and solution viscosity. The corresponding changes in either just the variable light (VL) or variable heavy (VH) chain showed only a partial decrease in viscosity, whereas changes in both VL and VH chains resulted in a dramatic reduction in viscosity. The converse case where the VL and VH chains of MAb2 were made to look like MAb1 did not self-associate or show increased viscosity. CONCLUSIONS:Exposed charged residues in the CDR of MAb1 are critical in determining the self-associating and highly viscous behavior observed at high concentrations.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Yadav S,Sreedhara A,Kanai S,Liu J,Lien S,Lowman H,Kalonia DS,Shire SJdoi
10.1007/s11095-011-0410-0subject
Has Abstractpub_date
2011-07-01 00:00:00pages
1750-64issue
7eissn
0724-8741issn
1573-904Xjournal_volume
28pub_type
杂志文章abstract：:The new generation of nanotechnology-based drug formulations is challenging the accepted ways of cancer treatment. Multi-functional nanomaterial constructs have the capability to be delivered directly to the tumor site and eradicate cancer cells selectively, while sparing healthy cells. Tailoring of the nano-construct...
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journal_title：Pharmaceutical research
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更新日期：2008-12-01 00:00:00
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journal_title：Pharmaceutical research
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更新日期：2004-02-01 00:00:00
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更新日期：1999-06-01 00:00:00
