Structural Analysis Quick Facts
The Problem: Structural information is a key for deciphering biological activity. All biological information resides in the sequence and three-dimensional shape of biomolecules - yet its routine quantification remains elusive for most applications in drug discovery and biotechnology. There is a critical need for rapid, simple-to-use techniques for structural analysis of biologics.
The Solution: Structural Signature Technology is a pioneering technique for fingerprint-like analysis of biologics. The technique readily compares and classifies product samples against known (well-characterized) examples of the same.
Key Benefits:
- Simple, inexpensive, automated structure-based product classification
- Adaptable to in-process quality control, including PAT
- Uses in stability, consistency, release, comparability, similarity and other applications
- Direct and close relationship to functional information via structure-function relationship
Validated Examples:
- Detection of a single residue change and sequence modification in peptides and proteins
- Classification of conformational changes induced by binding of different ligands, such as agonist vs. antagonist
- Quantification of the ratio of two isoforms directly in a mixture without pre-separation
- Determination of the biological efficacy of microheterogeneous biological products in quality-control applications
- Evaluation of the effects of excipients on the conformation of a protein
- Detection of chemical modifications to the structure, such as oxidation and deamidation
- Detection of aggregation of a peptide/protein, including non-covalent aggregation
- Monitoring of lot-to-lot consistency and comparison of products manufactured under changed conditions
- Determination of biosimilarity and detection of counterfeit products
Methodology: The sensitivity of the Structural Signature Technology relies on the unique ability of customized aqueous partitioning to detect very small structural changes in biologics. Its specificity comes from integrating information from multiple partitioning systems of different degrees of sensitivity to different structural changes. In a sense, the technology could be described as solvent spectroscopy, in which the aqueous solvent is being varied to probe different aspects of the structure under consideration. The process is automated using the Automated Structure Workstation (ASW).
