RESUMEN

Using genome mining, a new cytotoxic peptide named curacozole was isolated from Streptomyces curacoi. Through ESI-MS and NMR analyses, curacozole was determined to be a macrocyclic peptide containing two isoleucine, two thiazole and three oxazole moieties. Curacozole exhibited potent cytotoxic activity against HCT116 and HOS cancer cells. The proposed biosynthetic gene cluster of curacozole was identified and compared with that of the related compound YM-216391.

Asunto(s)

Antineoplásicos/farmacología , Genoma Bacteriano , Compuestos Macrocíclicos/farmacología , Péptidos/farmacología , Streptomyces/química , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Vías Biosintéticas/genética , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Minería de Datos , Humanos , Compuestos Macrocíclicos/química , Compuestos Macrocíclicos/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Péptidos/química , Péptidos/genética , Péptidos/aislamiento & purificación , Espectrometría de Masa por Ionización de Electrospray , Streptomyces/genética

RESUMEN

We attached d-Ala residues to cross-linked helical peptides based on the pro-apoptotic protein Bad at their C-termini. The d-Ala attachment had little influence on the secondary structures and binding abilities against Bcl-XL. The d-Ala attached helical peptides were much more stable in cells than original ones and efficiently induced apoptosis of the cells.