@article{5f04935dc9a5455ca4a9eb1454e8783d,
title = "Cold Denaturation of Proteins in the Absence of Solvent: Implications for Protein Storage**",
abstract = "The effect of temperature on the stability of proteins is well explored above 298 K, but harder to track experimentally below 273 K. Variable-temperature ion mobility mass spectrometry (VT IM-MS) allows us to measure the structure of molecules at sub-ambient temperatures. Here we monitor conformational changes that occur to two isotypes of monoclonal antibodies (mAbs) on cooling by measuring their collision cross sections (CCS) at discrete drift gas temperatures from 295 to 160 K. The CCS at 250 K is larger than predicted from collisional theory and experimental data at 295 K. This restructure is attributed to change in the strength of stabilizing intermolecular interactions. Below 250 K the CCS of the mAbs increases in line with prediction implying no rearrangement. Comparing data from isotypes suggest disulfide bridging influences thermal structural rearrangement. These findings indicate that in vacuo deep-freezing minimizes denaturation and maintains the native fold and VT IM-MS measurements at sub ambient temperatures provide new insights to the phenomenon of cold denaturation.",
keywords = "Cold Denaturation, Monoclonal Antibodies, Protein Folding, Structure–Activity Relationships, Variable-Temperature Ion Mobility",
author = "Norgate, {Emma L.} and Rosie Upton and Kjetil Hansen and Bruno Bellina and C. Brookes and Argyris Politis and Barran, {Perdita E.}",
note = "Funding Information: This work has been funded by a Research Impact Scholarship funded by alumni of the University of Manchester and Bristol-Myers Squibb for a CASE studentship awarded to E.N., a BBSRC Industrial Case Studentship awarded to R.U. in collaboration with Covance Laboratories and by the Leverhulme Trust (RPG-2019-178). Instrumentation was supported by Waters Corp. MS Vision, EPSRC (EP/T019328/1, GR/S77639/01) and BBSRC (BB/L01646X/1 BB/L015048/1 BB/L002655/1) awards and a lot of hard work and sweat. Funding Information: This work has been funded by a Research Impact Scholarship funded by alumni of the University of Manchester and Bristol‐Myers Squibb for a CASE studentship awarded to E.N., a BBSRC Industrial Case Studentship awarded to R.U. in collaboration with Covance Laboratories and by the Leverhulme Trust (RPG‐2019‐178). Instrumentation was supported by Waters Corp. MS Vision, EPSRC (EP/T019328/1, GR/S77639/01) and BBSRC (BB/L01646X/1 BB/L015048/1 BB/L002655/1) awards and a lot of hard work and sweat. Publisher Copyright: {\textcopyright} 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.",
year = "2022",
month = jun,
day = "20",
doi = "10.1002/anie.202115047",
language = "English",
volume = "61",
journal = "Angewandte Chemie - International Edition",
issn = "1433-7851",
publisher = "WILEY-BLACKWELL",
number = "25",
}