Dynamics of Intact Immunoglobulin G Explored by Drift-Tube Ion-Mobility Mass Spectrometry and Molecular Modeling

K J Pacholarz; M Porrini; R A Garlish; R J Burnley; R J Taylor; A J Henry; P E Barran

doi:10.1002/anie.201402863

Dynamics of Intact Immunoglobulin G Explored by Drift-Tube Ion-Mobility Mass Spectrometry and Molecular Modeling

K J Pacholarz, M Porrini, R A Garlish, R J Burnley, R J Taylor, A J Henry, P E Barran

Research output: Contribution to journal › Article › peer-review

Abstract

Collision cross-sections (CCS) of immunoglobulins G1 and G4 have been determined using linear drift-tube ion-mobility mass spectrometry. Intact antibodies and Fc-hinge fragments present with a larger range of CCS than proteins of comparable size. This is rationalized with MD simulations, which indicate significant in vacuo dynamics between linked folded domains. The IgG4 subclass presents over a wider CCS range than the IgG1 subclass.

Original language	English
Pages (from-to)	7765-7769
Number of pages	5
Journal	ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume	53
Issue number	30
DOIs	https://doi.org/10.1002/anie.201402863
Publication status	Published - 2014

Keywords

conformation analysis
immunoglobulin g
mass spectrometry
molecular dynamics
protein structures
fab-arm exchange
monoclonal-antibody
therapeutic antibodies
segmental flexibility
human-igg
crystals
isoforms

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10.1002/anie.201402863

http://www.ncbi.nlm.nih.gov/pubmed/24916519

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title = "Dynamics of Intact Immunoglobulin G Explored by Drift-Tube Ion-Mobility Mass Spectrometry and Molecular Modeling",

abstract = "Collision cross-sections (CCS) of immunoglobulins G1 and G4 have been determined using linear drift-tube ion-mobility mass spectrometry. Intact antibodies and Fc-hinge fragments present with a larger range of CCS than proteins of comparable size. This is rationalized with MD simulations, which indicate significant in vacuo dynamics between linked folded domains. The IgG4 subclass presents over a wider CCS range than the IgG1 subclass.",

keywords = "conformation analysis, immunoglobulin g, mass spectrometry, molecular dynamics, protein structures, fab-arm exchange, monoclonal-antibody, therapeutic antibodies, segmental flexibility, human-igg, crystals, isoforms",

author = "Pacholarz, {K J} and M Porrini and Garlish, {R A} and Burnley, {R J} and Taylor, {R J} and Henry, {A J} and Barran, {P E}",

note = "Pacholarz, Kamila J Porrini, Massimiliano Garlish, Rachel A Burnley, Rebecca J Taylor, Richard J Henry, Alistair J Barran, Perdita E eng 1008655/Medical Research Council/United Kingdom Medical Research Council/United Kingdom Research Support, Non-U.S. Gov't Germany International ed. in English 2014/06/12 06:00 Angew Chem Int Ed Engl. 2014 Jul 21;53(30):7765-9. doi: 10.1002/anie.201402863. Epub 2014 Jun 10.",

year = "2014",

doi = "10.1002/anie.201402863",

language = "English",

volume = "53",

pages = "7765--7769",

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publisher = "John Wiley & Sons Ltd",

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T1 - Dynamics of Intact Immunoglobulin G Explored by Drift-Tube Ion-Mobility Mass Spectrometry and Molecular Modeling

AU - Pacholarz, K J

AU - Porrini, M

AU - Garlish, R A

AU - Burnley, R J

AU - Taylor, R J

AU - Henry, A J

AU - Barran, P E

N1 - Pacholarz, Kamila J Porrini, Massimiliano Garlish, Rachel A Burnley, Rebecca J Taylor, Richard J Henry, Alistair J Barran, Perdita E eng 1008655/Medical Research Council/United Kingdom Medical Research Council/United Kingdom Research Support, Non-U.S. Gov't Germany International ed. in English 2014/06/12 06:00 Angew Chem Int Ed Engl. 2014 Jul 21;53(30):7765-9. doi: 10.1002/anie.201402863. Epub 2014 Jun 10.

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N2 - Collision cross-sections (CCS) of immunoglobulins G1 and G4 have been determined using linear drift-tube ion-mobility mass spectrometry. Intact antibodies and Fc-hinge fragments present with a larger range of CCS than proteins of comparable size. This is rationalized with MD simulations, which indicate significant in vacuo dynamics between linked folded domains. The IgG4 subclass presents over a wider CCS range than the IgG1 subclass.

AB - Collision cross-sections (CCS) of immunoglobulins G1 and G4 have been determined using linear drift-tube ion-mobility mass spectrometry. Intact antibodies and Fc-hinge fragments present with a larger range of CCS than proteins of comparable size. This is rationalized with MD simulations, which indicate significant in vacuo dynamics between linked folded domains. The IgG4 subclass presents over a wider CCS range than the IgG1 subclass.

KW - conformation analysis

KW - immunoglobulin g

KW - mass spectrometry

KW - molecular dynamics

KW - protein structures

KW - fab-arm exchange

KW - monoclonal-antibody

KW - therapeutic antibodies

KW - segmental flexibility

KW - human-igg

KW - crystals

KW - isoforms

U2 - 10.1002/anie.201402863

DO - 10.1002/anie.201402863

M3 - Article

SN - 1433-7851

VL - 53

SP - 7765

EP - 7769

JO - ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

JF - ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

IS - 30

ER -

Dynamics of Intact Immunoglobulin G Explored by Drift-Tube Ion-Mobility Mass Spectrometry and Molecular Modeling

Abstract

Keywords

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