Abstract
The long-term stability of protein therapeutics in the solid-state depends on the preservation of native structure during lyophilization and in the lyophilized powder. Proteins can reversibly or irreversibly unfold upon lyophilization, acquiring conformations susceptible to degradation during storage. Therefore, characterizing proteins in the dried state is crucial for the design of safe and efficacious formulations. This review summarizes the basic principles and applications of the analytical techniques that are commonly used to characterize protein structure, dynamics and conformation in lyophilized solids. The review also discusses the applications of recently developed mass spectrometry based methods (solid-state hydrogen deuterium exchange mass spectrometry (ssHDX-MS) and solid-state photolytic labeling mass spectrometry (ssPL-MS)) and their ability to study proteins in the solid-state at high resolution.
Keywords: Solid-state, lyophilization, protein structure, protein dynamics, protein conformations, protein stability, mass spectrometry, spectroscopy.
Current Pharmaceutical Design
Title:Characterizing Protein Structure, Dynamics and Conformation in Lyophilized Solids
Volume: 21 Issue: 40
Author(s): Balakrishnan S. Moorthy, Lavanya K. Iyer and Elizabeth M. Topp
Affiliation:
Keywords: Solid-state, lyophilization, protein structure, protein dynamics, protein conformations, protein stability, mass spectrometry, spectroscopy.
Abstract: The long-term stability of protein therapeutics in the solid-state depends on the preservation of native structure during lyophilization and in the lyophilized powder. Proteins can reversibly or irreversibly unfold upon lyophilization, acquiring conformations susceptible to degradation during storage. Therefore, characterizing proteins in the dried state is crucial for the design of safe and efficacious formulations. This review summarizes the basic principles and applications of the analytical techniques that are commonly used to characterize protein structure, dynamics and conformation in lyophilized solids. The review also discusses the applications of recently developed mass spectrometry based methods (solid-state hydrogen deuterium exchange mass spectrometry (ssHDX-MS) and solid-state photolytic labeling mass spectrometry (ssPL-MS)) and their ability to study proteins in the solid-state at high resolution.
Export Options
About this article
Cite this article as:
Moorthy S. Balakrishnan, Iyer K. Lavanya and Topp M. Elizabeth, Characterizing Protein Structure, Dynamics and Conformation in Lyophilized Solids, Current Pharmaceutical Design 2015; 21 (40) . https://dx.doi.org/10.2174/1381612821666151008150735
DOI https://dx.doi.org/10.2174/1381612821666151008150735 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
New Directions for Clinical Trials of Targeted Alpha Therapy for Metastatic Melanoma
Current Radiopharmaceuticals Imiquimod
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Perfluoroalkylsulfonyloxyisoflavones: Synthesis and Anti-Proliferation of HL-60
Letters in Organic Chemistry Biomolecular Pathogenesis of Borderline Ovarian Tumors: Focusing Target Discovery Through Proteogenomics
Current Cancer Drug Targets Extracellular Targeting of Synthetic Therapeutic Nucleic Acid Formulations
Current Gene Therapy The Structure and Main Functions of Aminopeptidase N
Current Medicinal Chemistry Comparison of Efficacy and Peripheral Neuropathy of Solvent-based Paclitaxel with Paclitaxel Poliglumex and NK105: A Systematic Review and Metaanalysis
Current Pharmaceutical Design Recent Advances in the Therapeutic Perspectives of Nutlin-3
Current Pharmaceutical Design Melanoma Immunotherapy: Past, Present, and Future
Current Pharmaceutical Design Tumor Hypoxia as a Modifier of DNA Strand Break and Cross-Link Repair
Current Molecular Medicine The Indolylcoumarin COUFIN Exhibits Potent Activity Against Renal Carcinoma Cells without Affecting Hematopoietic System
Anti-Cancer Agents in Medicinal Chemistry Management of Dyslipidaemia for the Prevention of Stroke: Clinical Practice Recommendations from the Lipid Association of India
Current Vascular Pharmacology Improved Prediction of Lysine Acetylation by Support Vector Machines
Protein & Peptide Letters A Disposable, Highly Sensitive Biosensing System: Determination of Haptoglobin as a Significant Acute Phase Biomarker
Current Analytical Chemistry Preparation of Knockout Extract for Determination of Really Active Compound Using MAb
Current Drug Discovery Technologies Aggregation-induced Emission-active Fluorescent Nanodot as a Potential Photosensitizer for Photodynamic Anticancer Therapy
Current Nanoscience Drug Metabolism and Pharmacokinetic Diversity of Ranunculaceae Medicinal Compounds
Current Drug Metabolism New Developments in Targeted Analysis of Protein Posttranslational Modifications
Current Proteomics DeepSSPred: A Deep Learning Based Sulfenylation Site Predictor Via a Novel nSegmented Optimize Federated Feature Encoder
Protein & Peptide Letters The Use of SIFT-MS to Investigate Headspace Aldehydes as Markers of Lipid Peroxidation
Current Analytical Chemistry