Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Más filtros

Banco de datos
Tipo del documento
Asunto de la revista
País de afiliación
Intervalo de año de publicación
1.
Anal Chem ; 96(12): 4756-4763, 2024 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-38326990

RESUMEN

The integrity of a higher order structure (HOS) is an essential requirement to ensure the efficacy, stability, and safety of protein therapeutics. Solution-state nuclear magnetic resonance (NMR) occupies a unique niche as one of the most promising methods to access atomic-level structural information on soluble biopharmaceutical formulations. Another major class of drugs is poorly soluble, such as microcrystalline suspensions, which poses significant challenges for the characterization of the active ingredient in its native state. Here, we have demonstrated a solid-state NMR method for HOS characterization of biopharmaceutical suspensions employing a selective excitation scheme under fast magic angle spinning (MAS). The applicability of the method is shown on commercial insulin suspensions at natural isotopic abundance. Selective excitation aided with proton detection and non-uniform sampling (NUS) provides improved sensitivity and resolution. The enhanced resolution enabled us to demonstrate the first experimental evidence of a phenol-escaping pathway in insulin, leading to conformational transitions to different hexameric states. This approach has the potential to serve as a valuable means for meticulously examining microcrystalline biopharmaceutical suspensions, which was previously not attainable in their native formulation states and can be seamlessly extended to other classes of biopharmaceuticals such as mAbs and other microcrystalline proteins.


Asunto(s)
Productos Biológicos , Insulina , Protones , Resonancia Magnética Nuclear Biomolecular/métodos , Proteínas/química
2.
J Magn Reson ; 328: 107002, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34052624

RESUMEN

In this paper, we present various chirp pulse sequences for implementing a broadband π rotation, which can serve as an ideal refocusing pulse element in a spin echo pulse sequence. These sequences are composed of three pulse elements each of which do adiabatic passage at rate a or 2a in either backward or forward direction. Various possible combinations are considered and different variants are presented. They all implement a broadband π rotation. We present the theory of such composite chirp sequences along with simulations and experiments.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA