RESUMEN
It is found that G-quadruplexes have important functions in biological systems, such as gene expression. Molecules which can stabilize the G-quadruplex structure may have potential application in regulating the expression of gene. A series of methylazacalix[n]pyridine (n=4, 6, 7, 8, 9) has been tested to stabilize the intermolecular human telomeric G-quadruplex (T12 and H12), intramolecular TBA, c-kit and bcl-2 G-quadruplex by CD denaturation experiments. The results showed that only methylazacalix[6]pyridine (MACP6) can stabilize the intermolecular G-quadruplex formed from the 12bp human telomere. Further studies evidenced that the shape-complementary binding mode was what contributed to the interaction between MACP6 and T12 G-quadruplex.
Asunto(s)
Calixarenos/farmacología , ADN/química , Excipientes/farmacología , G-Cuádruplex/efectos de los fármacos , Telómero/efectos de los fármacos , Dicroismo Circular , Humanos , Simulación del Acoplamiento Molecular , Desnaturalización de Ácido Nucleico/efectos de los fármacos , Telómero/químicaRESUMEN
The (NH)(m)(NMe)(4-m)-bridged calix[4]pyridines (m = 1-4) 19-23 were synthesized in excellent yields from deprotection of N-allyl groups of (NAllyl)(m)(NMe)(4-m)-bridged calix[4]pyridine derivatives 8 and 15-18, which were prepared in moderate yields by macrocyclic 2+2 and 1+3 coupling reactions between simple diamino- and dibromo-substituted fragments. In the solid state, (NH)(m)(NMe)(4-m)-bridged calix[4]pyridines adopted different 1,3-alternate conformations due to mainly the formation of varied conjugation systems of bridging NH units with their neighboring pyridines. In solution, all (NH)(m)(NMe)(4-m)-bridged calix[4]pyridines were very fluxional and the rates of interconversion of various conformational structures were very rapid relative to the NMR time scale. While (NH)(4)-bridged calix[4]pyridine 23 formed the strongest conjugation system, (NH)(2)(NMe)(2)-bridged calix[4]pyridine 21 acted as a selective fluorescence probe in the recognition of zinc(II) ion in solution with the dramatic enhancement of fluorescence intensity.
Asunto(s)
Piridinas/síntesis química , Ciclización , Estructura Molecular , Piridinas/química , EstereoisomerismoRESUMEN
A number of hydroxyl-substituted azacalix[4]pyridines were synthesized using Pd-catalyzed macrocyclic "2+2" and "3+1" coupling methods and the protection-deprotection strategy of hydroxyl group. While the conformation of the these hydroxyl-substituted azacalix[4]pyridines is fluxional in solution, in the solid state, they adopted shape-persistent 1,3-alternate conformations. Besides, X-ray analysis revealed that the existence of hydroxy groups on the para-position of pyridine facilitated the formation of solvent-bridged intermolecular hydrogen bonding for mono-hydroxyl-substituted while partial tautomerization for four-hydroxyl-substituted macrocycles, respectively. Taking the hydroxyl-substituted azacalix[4]pyridines as molecular platforms, multi-macrocycle-containing architectures and functional building blocks were constructed. The self-assembly behavior of the resulting building blocks was investigated in crystalline state.
RESUMEN
Large methylazacalix[n]pyridines (n = 6-9) were synthesized effectively from the Pd-catalyzed macrocyclic fragment coupling reactions between alpha,omega-dibrominated and alpha,omega-diaminated linear oligomers. As macrocyclic host molecules, they formed a 1:1 complex with fullerenes C(60) and C(70) with association constants ranging from 3 x 10(4) to 1 x 10(5) M(-1).
Asunto(s)
Calixarenos/síntesis química , Fulerenos/química , Piridinas/síntesis química , Calixarenos/química , Catálisis , Cristalografía por Rayos X , Modelos Moleculares , Conformación Molecular , Estructura Molecular , Paladio/química , Piridinas/químicaRESUMEN
Nucleic acid based molecular device is a developing research field which attracts great interests in material for building machinelike nanodevices. G-quadruplex, as a new type of DNA secondary structures, can be harnessed to construct molecular device owing to its rich structural polymorphism. Herein, we developed a switching system based on G-quadruplexes and methylazacalix[6]pyridine (MACP6). The induced circular dichroism (CD) signal of MACP6 was used to monitor the switch controlled by temperature or pH value. Furthermore, the CD titration, Job-plot, variable temperature CD and (1)H-NMR experiments not only confirmed the binding mode between MACP6 and G-quadruplex, but also explained the difference switching effect of MACP6 and various G-quadruplexes. The established strategy has the potential to be used as the chiral probe for specific G-quadruplex recognition.
Asunto(s)
Calixarenos/química , Computadores Moleculares , ADN/química , G-Cuádruplex , Oligonucleótidos/química , Dicroismo Circular , Proteínas de Unión al ADN/química , Concentración de Iones de Hidrógeno , Modelos Moleculares , Simulación del Acoplamiento Molecular , Resonancia Magnética Nuclear Biomolecular , TemperaturaRESUMEN
Calixaromatics have attracted much attention on molecular recognition owing to their flexible conformations, cavity structures, versatile recognition properties, and functions. However, conformational control of calixaromatics is still a challenging topic in the field of calixaromatics. Therefore, we explore the possibility to control the chirality of achiral calixaromatics, methylazacalix[6]pyridine (abbreviated as MACP6), by templating of DNA. We have found that MACP6 with opposite chirality can be achieved by controlling the secondary structure of bcl-2 2345 DNA. Furthermore, MACP6 with different chirality has been used to recognize fullerene derivatives in aqueous solution. Our results have provided a possible approach to construct chiral calixaromatics.
RESUMEN
A novel trend in G-quadruplex ligand design is to build a binder that is able to not only discriminate G-quadruplex from duplex-DNA, but also among various G-quadruplex structures. Methylazacalix[6]pyridine (MACP6), a new type of azacalixarene with flexible conformation, exhibits induced circular dichroism signals when interacted with most of G-quadruplexes. The intensities of the induced signals are strongly dependent on the topology of G-quadruplexes. Further evidence has shown that these signals can be ascribed to the preferred binding of MACP6 to the loops of G-quadruplexes, which rely on the nature of nucleotides in the loops.