| Texto completo | |
| Autor(es): Mostrar menos - |
Meneghetti, Maria C. Z.
;
Naughton, Lucy
;
O'Shea, Conor
;
Teki, Dindet S. E. Koffi
;
Chagnault, Vincent
;
Nader, Helena B.
;
Rudd, Timothy R.
;
Yates, Edwin A.
;
Kovensky, Jose
;
Miller, Gavin J.
;
Lima, Marcelo A.
Número total de Autores: 11
|
| Tipo de documento: | Artigo Científico |
| Fonte: | ACS OMEGA; v. N/A, p. 7-pg., 2022-07-08. |
| Resumo | |
Heparan sulfate (HS), a sulfated linear carbohydrate that decorates the cell surface and extracellular matrix, is ubiquitously distributed throughout the animal kingdom and represents a key regulator of biological processes and a largely untapped reservoir of potential therapeutic targets. The temporal and spatial variations in the HS structure underpin the concept of "heparanome " and a complex network of HS binding proteins. However, despite its widespread biological roles, the determination of direct structure-to-function correlations is impaired by HS chemical heterogeneity. Attempts to correlate substitution patterns (mostly at the level of sulfation) with a given biological activity have been made. Nonetheless, these do not generally consider higher-level conformational effects at the carbohydrate level. Here, the use of NMR chemical shift analysis, NOEs, and spin-spin coupling constants sheds new light on how different sulfation patterns affect the polysaccharide backbone geometry. Furthermore, the substitution of native O-glycosidic linkages to hydrolytically more stable S-glycosidic forms leads to observable conformational changes in model saccharides, suggesting that alternative chemical spaces can be accessed and explored using such mimetics. Employing a series of systematically modified heparin oligosaccharides (as a proxy for HS) and chemically synthesized O-and S-glycoside analogues, the chemical space occupied by such compounds is explored and described. (AU) | |
| Processo FAPESP: | 20/04899-1 - Interação da proteína de superfície (spike protein) do SARS-CoV-2 com heparina: potencial terapêutico |
| Beneficiário: | Helena Bonciani Nader |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 17/14179-3 - Tráfego vesicular na biossíntese do heparam sulfato |
| Beneficiário: | Ivarne Luis dos Santos Tersariol |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 19/19298-6 - Desvendando a influência do tráfego vesicular na regulação da biossíntese do heparam sulfato |
| Beneficiário: | Maria Cecília Zorél Meneghetti |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |