Confirmation of the Disulfide Connectivity and Strategies for Chemical Synthesis of the Four-Disulfide-Bond-Stabilized Aspergillus giganteus Antifungal Protein, AFP

Emerging fungal infections require new, more efficient antifungal agents and therapies. AFP, a protein from Aspergillus giganteus with four disulfide bonds, is a promising candidate because it selectively inhibits the growth of filamentous fungi. In this work, the reduced form of AFP was prepared us...

Teljes leírás

Elmentve itt :
Bibliográfiai részletek
Szerzők: Váradi Györgyi
Batta Gyula
Galgóczi László Norbert
Hajdu Dorottya Zsuzsanna
Fizil Ádám
Czajlik András
Virágh Máté
Kele Zoltán
Meyer Vera
Jung Sascha
Marx Florentine
Tóth Gábor
Dokumentumtípus: Cikk
Megjelent: 2023
Sorozat:JOURNAL OF NATURAL PRODUCTS 86 No. 4
Tárgyszavak:
doi:10.1021/acs.jnatprod.2c00954

mtmt:33676645
Online Access:http://publicatio.bibl.u-szeged.hu/28252
Leíró adatok
Tartalmi kivonat:Emerging fungal infections require new, more efficient antifungal agents and therapies. AFP, a protein from Aspergillus giganteus with four disulfide bonds, is a promising candidate because it selectively inhibits the growth of filamentous fungi. In this work, the reduced form of AFP was prepared using native chemical ligation. The native protein was synthesized via oxidative folding with uniform protection for cysteine thiols. AFP's biological activity depends heavily on the pattern of natural disulfide bonds. Enzymatic digestion and MS analysis provide proof for interlocking disulfide topology (abcdabcd) that was previously assumed. With this knowledge, a semi-orthogonal thiol protection method was designed. By following this strategy, out of a possible 105, only 6 disulfide isomers formed and 1 of them proved to be identical with the native protein. This approach allows the synthesis of analogs for examining structure-activity relationships and, thus, preparing AFP variants with higher antifungal activity.
Terjedelem/Fizikai jellemzők:782-790
ISSN:0163-3864