Water-Soluble Cationic Metalloporphyrins: Specific G-Quadruplex-Stabilizing Ability and Reversible Chirality of Aggregates Induced by AT-Rich DNA.

Cu-TMPipPrOPP and Zn-TMPipPrOPP, two new cationic metallo derivatives of TMPipPrOPP (5,10,15,20-tetrakis{4-[3-(1-methyl-1-piperidinyl)propoxy]phenyl}porphyrin), a porphyrin with four bulky side chains, were synthesized and characterized. The interactions of the new metalloporphyrins with structurally different DNAs were then compared with those of TMPipPrOPP. The introduction of bulky side chains provides the porphyrin derivatives with excellent binding specificity for G-quadruplex DNA, which is reflected by (1) the significantly different optical responses of TMPipPrOPP toward G-quadruplexes in comparison with single-stranded and duplex DNAs and (2) the ability of the three porphyrin derivatives to effectively stabilize G-quadruplexes, with no or little effect on the stability of duplex DNA. TMPipPrOPP can achieve colorimetric and fluorescent discrimination of G-quadruplexes from single-stranded and duplex DNAs with extraordinary high specificity. Due the presence of metal ions, Cu-TMPipPrOPP and Zn-TMPipPrOPP are deprived of the ability for optical G-quadruplex recognition but show enhanced ability to stabilize G-quadruplexes. In addition, because of the presence of the four cationic side chain substituents, the three porphyrin derivatives can form chiral aggregates via electrostatic interactions along the surface of structurally diverse DNAs. The chirality of aggregates formed by TMPipPrOPP is not changed by the nature of the template DNAs, whereas aggregates formed by Cu-TMPipPrOPP and Zn-TMPipPrOPP in the presence of adenine-thymine (AT) rich duplex DNA show completely inverted chirality in comparison with those formed in the presence of other DNAs. Interestingly, the chirality of the aggregates can be reversibly switched many times by alternating the ratio of Cu-TMPipPrOPP (or Zn-TMPipPrOPP) to AT-rich duplex DNA.

Optimization of strand displacement amplification-sensitized G-quadruplex DNAzyme-based sensing system and its application in activity detection of uracil-DNA glycosylase.

As an isothermal nucleic acid amplification technique, strand displacement amplification (SDA) reaction has been introduced in G-quadruplex DNAzyme-based sensing system to improve the sensing performance. To further provide useful information for the design of SDA-amplified G-quadruplex DNAzyme-based sensors, the effects of nicking site number in SDA template DNA were investigated. With the increase of the nicking site number from 1 to 2, enrichment of G-quadruplex DNAzyme by SDA is changed from a linear amplification to an exponential amplification, thus greatly increasing the amplification efficiency and subsequently improving the sensing performance of corresponding sensing system. The nicking site number cannot be further increased because more nicking sites might result in high background signals. However, we demonstrated that G-quadruplex DNAzyme enrichment efficiency could be further improved by introducing a cross-triggered SDA strategy, in which two templates each has two nicking sites are used. To validate the proposed cross-triggered SDA strategy, we used it to develop a sensing platform for the detection of uracil-DNA glycosylase (UDG) activity. The sensor enables sensitive detection of UDG activity in the range of 1 × 10(-4)-1 U/mL with a detection limit of 1 × 10(-4)U/mL.

Simple synthesis of amino acid-functionalized hydrophilic upconversion nanoparticles capped with both carboxyl and amino groups for bimodal imaging.

The development of multimodal imaging probes carrying more than one modifiable site is very important in medical diagnosis. Herein, we demonstrate that amino acids, including acidic, neutral and basic amino acids, can be used as stabilizers and functional agents for the simple, one-step hydrothermal synthesis of hydrophilic upconversion nanoparticles (UCNPs) with a pure hexagonal phase and strong upconversion luminescence (UCL). The surface of the as-prepared UCNPs was capped with both carboxyl and amino groups, which not only provided the NPs with good dispersity in water, but also made further conjugation with two different biomolecules (e.g. targeted molecules and functional agents) possible. By co-doping different lanthanide ions, amino acid-functionalized UCNPs with different-colored UCL and different functions were obtained. For example, aspartate (Asp)-functionalized NaLuF4 co-doped with Tm3+ and Gd3+ not only emitted strong UCL in the range of the biological transparent window, but also has great potential as a T1-weighted magnetic resonance (MR) imaging contrast agent. The as-prepared Asp-NaLuF4:Gd/Yb/Tm UCNPs were successfully used in the UCL/MR bimodal in vivo imaging of nude mice.

Two cationic porphyrin isomers showing different multimeric G-quadruplex recognition specificity against monomeric G-quadruplexes.

Ligands that can interact specifically with telomeric multimeric G-quadruplexes could be developed as promising anticancer drugs with few side effects related to other G-quadruplex-forming regions. In this paper, a new cationic porphyrin derivative, m-TMPipEOPP, was synthesized and characterized. Its multimeric G-quadruplex recognition specificity under molecular crowding conditions was compared to its isomer p-TMPipEOPP. The slight structural difference accounts for different multimeric G-quadruplex recognition specificity for the two isomers. p-TMPipEOPP can barely discriminate between multimeric and monomeric G-quadruplexes. By contrast, m-TMPipEOPP can bind with multimeric but not with monomeric G-quadruplexes. p-TMPipEOPP might bind to multimeric G-quadruplexes by two modes: sandwich-like end-stacking mode and pocket-dependent intercalative mode. Increasing the pocket size between adjacent two G-quadruplex units is beneficial for the latter mode. m-TMPipEOPP might bind to multimeric G-quadruplexes by a side binding mode, which confers m-TMPipEOPP with higher multimeric G-quadruplex recognition specificity compared to p-TMPipEOPP. m-TMPipEOPP increases the stability of multimeric G-quadruplex under both dilute and molecular crowding conditions but its G-quadruplex-stabilizing ability is a little weaker than p-TMPipEOPP. These results provide important information for the design of highly specific multimeric G-quadruplex ligands. Another interesting finding is that pocket size is an important factor in determining the stability of multimeric G-quadruplexes.