Protein Structure Analysis using One-Step Tyrosine Conjugation

This invention includes methods and systems for detecting, comparing, or evaluating proteins in an folded conformation, a particular bound state, or an aggregate state, and methods and systems for comparing amounts of labeling of a protein in a natural or control conformation and a denatured conformation. The methods of this invention may be used for a variety of applications including but not limited to evaluation of protein aggregates levels related to a particular disease (e.g., aggregate-associated disease, etc.), for study of disease progression, drug development for therapeutics at various stages of disease progression, or for diagnostic purposes.

Background:
Current standards of proteopathy disease diagnoses, such as El Escorial criteria for ALS, lack sensitivity and are unable to quantify disease progression. Lack of tools to evaluate disease progression may limit therapeutic development and opportunities for effective clinical application. The novel technology presented here addresses these issues by increasing the sensitivity and reliability of detecting structural proteopathies.

Applications:

• Characterize progression of proteopathy for drug development
• Clinical evaluation of progression of disease
• Amyotrophic Lateral Sclerosis (ALS) research and drug discovery
• Research and drug discovery for other protein misfolding diseases: cystic fibrosis, amyloidosis, Huntington's disease, and many others

Advantages:

• Increased sensitivity and reliability
• Covalent binding
• Quantitative method
• Does not require specialized equipment or training 
• Can be used to characterize progression of disease