Proton-Detected Solid-State NMR Spectroscopy of Natural-Abundance Peptide and Protein Pharmaceuticals

摘要

Over 80% of pharmaceutical products on the market,including many biopharmaceuticals,are in various solid forms.Solid-state NMR(SSNMR)provides atomic-resolution structural insight to such materials,and therefore is recognized as a powerful analytical approach to analyze formulation chemistry in pharmaceutical products.Dramatic progress in SSNMR over the last decade has enabled the determination of structures for several proteins,with the assistance of ~(13)C and ~(15)N isotope enrichment.However,owing to the limited experimental sensitivity inherent in the low natural abundance of ~(13)C(1.07%)and ~(15)N(0.368%),the application in pharmaceutical SSNMR research has been limited to small molecules.Furthermore,the one-dimensional ~(13)C spectra commonly acquired for small-molecule drugs have insufficient resolution for larger peptide and protein pharmaceuticals.