Systematic strategy for the development of glycosyltransferase inhibitors: diversity-oriented synthesis of FUT8 inhibitors

Manabe, Yoshiyuki ; Fukase, Koichi ; Hizume, Koki ; Takakura, Yohei ; Takamatsu, Shinji ; Miyoshi, Eiji ; Kamada, Yoshihiro ; Hurtado-Guerrero, Ramón

Resumen: Glycans control various biological processes, depending on their structures. Particularly, core fucose, formed by α1,6-fucosyltransferase (FUT8), has a substantial influence on multiple biological processes. In this study, we investigated the development of FUT8 inhibitors with structural elements encompassing both the glycosyl donor (GDP-fucose) and acceptor (N-glycan) of FUT8. To efficiently optimize the structure of FUT8 inhibitors, we employed a strategy involving fragmentation of the target structure, followed by a structure optimization using a diversity-oriented synthesis approach. This study proposes an efficient strategy to accelerate the structural optimization of middle molecules.

Idioma: Inglés

DOI: 10.1055/a-2221-9096

Año: 2024

Publicado en: SYNLETT 35, 11 (2024), 1273-1278
ISSN: 0936-5214

Factor impacto JCR: 1.4 (2024)

Categ. JCR: CHEMISTRY, ORGANIC rank: 42 / 57 = 0.737 (2024) - Q3 - T3

Factor impacto SCIMAGO: 0.437 - Organic Chemistry (Q3)

Financiación: info:eu-repo/grantAgreement/ES/AEI/PID2019-105451GB-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN AEI/PID2022-136362NB-I00

Tipo y forma: (PostPrint)