Stereospecific interactions between histidine and monoclonal antibodies

Youngbin Baek, Parinaz Emami, Nripen Singh, Andrew Ilott, Erinc Sahin, Andrew Zydney

Research output: Contribution to journalArticle

Abstract

Histidine is a frequently used buffer in the final formulation of many commercialized monoclonal antibodies (mAbs), with histidine helping to stabilize the antibody during storage in addition to its buffering function. The objective of this study was to examine the stereospecificity of any histidine-antibody interactions using a combination of experimental studies and molecular dynamics simulations. Isothermal titration calorimetry provided evidence of weak stereospecific interactions, with the antibody showing approximately two to four additional interaction sites for d- versus l-histidine. The greater interactions with d-histidine were confirmed by measurements of the net protein charge using electrophoretic light scattering. The reduction in the net negative charge of the antibody in d-histidine led to significantly different behavior during diafiltration due to Donnan exclusion effects. Molecular dynamics simulations corroborated the presence of additional d-histidine interaction sites. These results provide the first demonstration of weak stereospecific interactions between l- and d-histidine and a mAb and the implications of these interactions for antibody formulation.

Original languageEnglish (US)
Pages (from-to)2632-2639
Number of pages8
JournalBiotechnology and bioengineering
Volume116
Issue number10
DOIs
StatePublished - Oct 1 2019

Fingerprint

Monoclonal antibodies
Histidine
Antibodies
Monoclonal Antibodies
Molecular dynamics
Molecular Dynamics Simulation
Computer simulation
Calorimetry
Titration
Light scattering
Demonstrations
Proteins
Buffers
Light

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

Baek, Youngbin ; Emami, Parinaz ; Singh, Nripen ; Ilott, Andrew ; Sahin, Erinc ; Zydney, Andrew. / Stereospecific interactions between histidine and monoclonal antibodies. In: Biotechnology and bioengineering. 2019 ; Vol. 116, No. 10. pp. 2632-2639.
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Stereospecific interactions between histidine and monoclonal antibodies. / Baek, Youngbin; Emami, Parinaz; Singh, Nripen; Ilott, Andrew; Sahin, Erinc; Zydney, Andrew.

In: Biotechnology and bioengineering, Vol. 116, No. 10, 01.10.2019, p. 2632-2639.

Research output: Contribution to journalArticle

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