Next Article in Journal
Total Synthesis and Anti-Viral Activities of an Extract of Radix isatidis
Next Article in Special Issue
Comparative Study of the Structural and Vibroelectronic Properties of Porphyrin and Its Derivatives
Previous Article in Journal
Two New Coumarins from Talaromyces flavus
Previous Article in Special Issue
Au-Nanomaterials as a Superior Choice for Near-Infrared Photothermal Therapy
Article Menu

Export Article

Open AccessArticle
Molecules 2014, 19(12), 20888-20905; doi:10.3390/molecules191220888

Combined Dynamic Light Scattering and Raman Spectroscopy Approach for Characterizing the Aggregation of Therapeutic Proteins

Malvern Biosciences Inc., 7221 Lee Deforest Drive, Suite 300, Columbia, MD 21046, USA
*
Author to whom correspondence should be addressed.
Received: 7 November 2014 / Revised: 2 December 2014 / Accepted: 5 December 2014 / Published: 12 December 2014
(This article belongs to the Special Issue Advances of Vibrational Spectroscopic Technologies in Life Sciences)
View Full-Text   |   Download PDF [2157 KB, uploaded 12 December 2014]   |  

Abstract

Determination of the physicochemical properties of protein therapeutics and their aggregates is critical for developing formulations that enhance product efficacy, stability, safety and manufacturability. Analytical challenges are compounded for materials: (1) that are formulated at high concentration, (2) that are formulated with a variety of excipients, and (3) that are available only in small volumes. In this article, a new instrument is described that measures protein secondary and tertiary structure, as well as molecular size, over a range of concentrations and formulation conditions of low volume samples. Specifically, characterization of colloidal and conformational stability is obtained through a combination of two well-established analytical techniques: dynamic light scattering (DLS) and Raman spectroscopy, respectively. As the data for these two analytical modalities are collected on the same sample at the same time, the technique enables direct correlation between them, in addition to the more straightforward benefit of minimizing sample usage by providing multiple analytical measurements on the same aliquot non-destructively. The ability to differentiate between unfolding and aggregation that the combination of these techniques provides enables insights into underlying protein aggregation mechanisms. The article will report on mechanistic insights for aggregation that have been obtained from the application of this technique to the characterization of lysozyme, which was evaluated as a function of concentration and pH. View Full-Text
Keywords: dynamic light scattering; Raman spectroscopy; lysozyme; protein aggregation; self-assembly dynamic light scattering; Raman spectroscopy; lysozyme; protein aggregation; self-assembly
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Lewis, E.N.; Qi, W.; Kidder, L.H.; Amin, S.; Kenyon, S.M.; Blake, S. Combined Dynamic Light Scattering and Raman Spectroscopy Approach for Characterizing the Aggregation of Therapeutic Proteins. Molecules 2014, 19, 20888-20905.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top