Conformational significance of EH21A1–A4, phenolic derivatives of geldanamycin, for Hsp90 inhibitory activity

Hsp90 is an attractive chemotherapeutic target because it is essential to maturation of multiple oncogenes. We describe the conformational significance of EH21A1–A4, phenolic derivatives of geldanamycin isolated from Streptomyces sp. Their native free structures are similar to the active form of geldanamycin bound to Hsp90 protein. Their conformational character is a probable reason for their high-affinity binding. Lack of toxic benzoquinone in EH21A1–A4 also adds to their potential as lead compounds for anti-tumor drugs.

Graphical abstractEH21A1–A4, phenolic derivatives of geldanamycin were isolated from Streptomyces sp. Their native structures are similar to the active form of geldanamycin. The conformational character is a probable reason for their high affinity to Hsp90 protein.Figure optionsDownload full-size imageDownload as PowerPoint slide