RESUMEN
A DNA-multiple drug complex, d(ACGTAGCTACGT)(2):[actinomycin D, (echinomycin)(2)] has been crystallized. The crystals belong to the monoclinic space group C2, with unit-cell parameters a = 85.6, b = 72.8, c = 56.6 A, beta = 101.5 degrees at 93 K and Z = 8. The crystal diffracted to 3.0 A resolution along the DNA fiber axis and to 3.5 A resolution in other directions. The Patterson maps indicate that all complexes in the crystal are oriented along their helical axes in the [101;] direction.
Asunto(s)
Dactinomicina/química , Equinomicina/química , Oligodesoxirribonucleótidos/química , Cristalización , Cristalografía por Rayos X , Dactinomicina/metabolismo , Equinomicina/metabolismo , Sustancias Macromoleculares , Modelos Moleculares , Conformación Molecular , Estructura Molecular , Oligodesoxirribonucleótidos/metabolismo , Quinoxalinas/química , Quinoxalinas/metabolismoRESUMEN
Natural analogues (D, C2, and VII) of actinomycin inhibit Grb2 SH2 domain binding with phosphopeptide-derived from Shc in vitro and in intracellular system. To study structure-activity relationships, 13 actinomycin analogues were synthesized and we found that the inhibition activity depended on the substituents of cyclic peptide groups in actinomycin and two analogues with Tyr residue are the most potent inhibitors with IC50 value of 0.5 and 0.8 microM, respectively.