Cellular Uptake of PNA−Terpyridine Conjugates and Its Enhancement by Zn²⁺ Ions

Abstract

Conjugation of usually impermeable peptide nucleic acids (PNA) to the chelator 2,2':6',2' '-terpyridine strongly promotes cellular and nuclear uptake by cultured HeLa cells. Cellular accumulation is further enhanced in the presence of extracellular Zn2+.

Metal-containing peptide nucleic acid conjugates

“…166 With this in mind, they reported the synthesis of a series of cyclen and dpa derivatives, their subsequent attachment to the 5´-amino end of 12-mer PNA sequences complementary to the bulge region of the HIV-1 TAR stem loop RNA (Figure 17b). 163 Thermal denaturation experiments were performed with a small oligonucleotide transcript of the TAR sequence and some single stranded RNA and DNA oligonucleotides, both in the presence and absence of Zn(II) ions.…”

Ratiometric Fluorescence Recognition for Pyrophosphate on the Basis of Terpyridine Derivative

“…9,23 The coordination of the tpy moiety with Cd(II) was also the reason for the fluorescence enhancement of aptpy at 397 nm. 19 The maximum intensity of fluorescence at 397 nm was obtained at a metal/ligand ratio of 1 (Fig. 2B).…”

“…18,19 Herein, the cadmium complex of the tpy derivative, 4′-(aminomethylphenyl)-2,2′:6′,2″-terpyridine (aptpy), has been employed for the highly selective recognition of PPi based on the ratiometric fluorescence measurement. When added with cadmium, the emission of aptpy at 358 nm was greatly enhanced and red shifted to 397 nm due to the complexation-induced ICT process, and then blue shifted to 349 nm with a further addition of PPi.…”

Specific uptake and interactions of peptide nucleic acid derivatives with biomimetic membranes

“…13 Although much attention has been focussed on the preparation of such constructs [37][38][39][40][41] and only recently have papers appeared which report the applications of non-radioactive metal 75 bioconjugates in living cells. [14][15][42][43][44] It is therefore important to understand the mechanism of uptake of these nucleotide analogues.…”

“…These include co-delivery with partial cDNA oligonucleotides, cationic lipids and lipophilic triphenylphosphonium (TPP) cations, and a few examples of chemical modifications of PNA oligomers with metal complexes. 6,8,[11][12][13][14][15] However, to date, the most promising 30 approach has been the conjugation of PNAs with cell penetrating peptides (CPP). 6,8,12 Although the mechanism of translocation of CPPs is not fully understood, their ability to successfully transport cargo (e.g., PNAs) into the cell makes them effective delivery agents.…”