Human CUL2 blocking peptide

The coordination compound of copper nitrate [CuL2(H2O)](NO3)(2) with 2-(N-acetylamino)-6-methylpyridine (L) of the composition [CuL2(H2O)](NO3)(2) has been prepared and investigated by single-crystal X-ray diffraction analysis and electron paramagnetic resonance (EPR) measurements. Crystalline samples, frozen solution in ethanol, thin films on quartz substrates and nanosized particles in mesoporous structures were investigated. The observed EPR spectra of [CuL2(H2O)](NO3)(2) with a mesoporous structure and a pore diameter of 4 nm demonstrates that only dimers are realized in this matrix, but in a mesoporous structure with a pore diameter of 9 nm, seed crystals are formed together with dimers.

The ability of four stable hemiaminals differently substituted in the phenyl ring and their complexes with Cu2+ ions to inhibit catalytic cleavage of the antigenomic delta ribozyme was compared. The hemiaminals were novel chiral derivatives of 1,2,4-triazole [i.e. (2,4-dinitrophenyl)(4H-1,2,4-triazol-4-ylamino) methanol (2,4-dnbald), (2-nitrophenyl)(4H-1,2,4-triazol-4-ylamino) methanol (2-nbald), (3-nitrophenyl)(4H-1,2,4-triazol-4-ylamino) methanol (3-nbald) and (4-nitrophenyl)(4H-1,2,4-triazol-4-ylamino) methanol (4-nbald)]. The complexes of nbalds with Cu2+ were characterized using UV and EPR methods and additionally, the formation of 2,4-dnbald-Cu2+ complex with CuL2 stoichiometry was confirmed by mass spectrometry. The data suggest that there are two ways in which nbalds and their Cu2+ complexes can influence catalytic cleavage of antigenomic delta ribozyme. The coordinated Cu2+ ions may play the role of new cationic ligands increasing the affinity of the complexes to the ribozyme. Such situation occurs in the case of 2- and 2,4-nbald. Their Cu2+ complexes decrease ribozyme cleavage rates twice more efficiently than uncomplexed compounds. Moreover, the Cu2+ complexes displace the catalytic divalent metal ions from their strong binding sites located in the ribozyme J4/2 region as shown by the Pb2+-induced cleavage approach. On the other hand, 3- and 4-nbald inhibit catalysis more strongly as compared to 2-nbald and 2,4-dnbald but the ribozyme cleavage rates are changed only slightly upon Cu2+ complexation. The mechanism of ribozyme inhibition by interfering with the formation of a correct ribozyme tertiary structure seems to operate in this case. (c) 2011 Elsevier Inc. All rights reserved.