Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

You’ve supercharged your research process with ACS and Mendeley!

STEP 1:
Click to create an ACS ID

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

MENDELEY PAIRING EXPIRED
Your Mendeley pairing has expired. Please reconnect
ACS Publications. Most Trusted. Most Cited. Most Read
My Activity
CONTENT TYPES

Figure 1Loading Img

Reversible Self-Association in Lactate Dehydrogenase during Freeze–Thaw in Buffered Solutions Using Neutron Scattering

  • Jayesh Sonje
    Jayesh Sonje
    Department of Pharmaceutics, College of Pharmacy, University of Minnesota, 308 Harvard St. SE, Minneapolis, Minnesota 55455, United States
    More by Jayesh Sonje
  • Seema Thakral
    Seema Thakral
    Department of Pharmaceutics, College of Pharmacy, University of Minnesota, 308 Harvard St. SE, Minneapolis, Minnesota 55455, United States
    Characterization Facility, University of Minnesota, Minneapolis, Minnesota 55455, United States
  • Susan Krueger*
    Susan Krueger
    Center for Neutron Research, National Institute of Standards and Technology, 100 Bureau Drive, Gaithersburg, Maryland 20899, United States
    *Email: [email protected]. Phone: 301-975-6734. Fax:301-921-9847.
  • , and 
  • Raj Suryanarayanan*
    Raj Suryanarayanan
    Department of Pharmaceutics, College of Pharmacy, University of Minnesota, 308 Harvard St. SE, Minneapolis, Minnesota 55455, United States
    *Email: [email protected]. Phone: (612) 624-9626. Fax: (612) 626-2125.
Cite this: Mol. Pharmaceutics 2021, 18, 12, 4459–4474
Publication Date (Web):October 28, 2021
https://doi.org/10.1021/acs.molpharmaceut.1c00666
Copyright © 2021 American Chemical Society

    Article Views

    610

    Altmetric

    -

    Citations

    LEARN ABOUT THESE METRICS
    Other access options
    Supporting Info (1)»

    Abstract

    Abstract Image

    The aims of this work were to evaluate the effect of freezing and thawing stresses on lactate dehydrogenase (LDH) stability under three conditions. (i) In a solution buffered with sodium phosphate (NaP; 10 and 100 mM). The selective crystallization of disodium hydrogen phosphate during freezing caused a pronounced pH shift. (ii) In a solution buffered with histidine, where there was no pH shift due to buffer salt crystallization. (iii) At different concentrations of LDH so as to determine the self-stabilizing ability of LDH. The change in LDH tetrameric conformation was measured by small-angle neutron scattering (SANS). The pH of the phosphate buffer solutions was monitored as a function of temperature to quantify the pH shift. The conditions of buffer component crystallization from solution were identified using low-temperature X-ray diffractometry. Dynamic light scattering (DLS) enabled us to determine the effect of freeze-thawing on the protein aggregation behavior. LDH, at a high concentration (1000 μg/mL; buffer concentration 10 mM), has a pronounced self-stabilizing effect and did not aggregate after five freeze–thaw cycles. At lower LDH concentrations (10 and 100 μg/mL), only with the selection of an appropriate buffer, irreversible aggregation could be avoided. While SANS provided qualitative information with respect to protein conformation, the insights from DLS were quantitative with respect to the particle size of the aggregates. SANS is the only technique which can characterize the protein both in the frozen and thawed states.

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. You can change your affiliated institution below.

    Supporting Information

    ARTICLE SECTIONS
    Jump To

    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.1c00666.

    • Guinier fits used to calculate Rg and I(0); SAXS data; plot of LDH surface charge; low-temperature XRD, and low-temperature pH measurements (PDF)

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    This article is cited by 7 publications.

    1. Jin Kyung Park, So-Jung Park, Byeongmoon Jeong. Poly(l-alanine-co-l-threonine succinate) as a Biomimetic Cryoprotectant. ACS Applied Materials & Interfaces 2023, 15 (50) , 58092-58102. https://doi.org/10.1021/acsami.3c11260
    2. Jinghan Li, Jayesh Sonje, Raj Suryanarayanan. Role of Poloxamer 188 in Preventing Ice-Surface-Induced Protein Destabilization during Freeze–Thawing. Molecular Pharmaceutics 2023, 20 (9) , 4587-4596. https://doi.org/10.1021/acs.molpharmaceut.3c00312
    3. Jayesh Sonje, Seema Thakral, Susan Krueger, Raj Suryanarayanan. Enabling Efficient Design of Biological Formulations Through Advanced Characterization. Pharmaceutical Research 2023, 46 https://doi.org/10.1007/s11095-023-03495-z
    4. Eva Rose M. Balog. Spectroscopic investigation of biomolecular dynamics using light scattering methods. 2023, 211-226. https://doi.org/10.1016/B978-0-323-99127-8.00011-8
    5. Paroma Chakravarty, Alekha Dash, Evgenyi Shalaev, Changquan Calvin Sun, Geoff G.Z. Zhang, Seema Thakral. Professor Raj Suryanarayanan: Scientist, Educator, Mentor, Family Man and Giant in Pharmaceutical Research. Journal of Pharmaceutical Sciences 2023, 112 (1) , 2-7. https://doi.org/10.1016/j.xphs.2022.10.032
    6. Tibo Duran, Bruna Minatovicz, Ryan Bellucci, Jun Bai, Bodhisattwa Chaudhuri. Molecular Dynamics Modeling Based Investigation of the Effect of Freezing Rate on Lysozyme Stability. Pharmaceutical Research 2022, 39 (10) , 2585-2596. https://doi.org/10.1007/s11095-022-03358-z
    7. Susan Krueger. Small-angle neutron scattering contrast variation studies of biological complexes: Challenges and triumphs. Current Opinion in Structural Biology 2022, 74 , 102375. https://doi.org/10.1016/j.sbi.2022.102375