This work highlights a novel method of coupling of nucleic acids through formation of an extraordinary stable, specific and fully reversible quadruplex-and-Mg2+ connection (QMC). QMC employs the monomolecular tetrahelical architecture of DNA and has two key components: (i) shape complementarity between QMC partners, which is introduced by specific modifications of the quadruplexes, and (ii) Mg2+ ions. The on-rate of QMC formation is between 105–106 M−1 s−1, while the off-rate is undetectable even at 80 °C. However, QMC dissociates rapidly upon removal of Mg2+ ions (i.e., by EDTA). QMC is characterized by high specificity, as even a single-nucleotide modification of one of the connectors inhibits complex-formation. QMC has the potential to revolutionize biotechnology by introducing a new class of capture molecules with major advantages over traditional systems such as streptavidin-biotin. The advantages include reversibility, multiplexing, higher stability and specificity, longer shelf life and low cost.