Multimerization rules for G-quadruplexes

Abstract

G-quadruplexes can multimerize under certain conditions, but the sequence requirements of such structures are not well understood. In this study, we investigated the ability of all possible variants of the central tetrad in a monomeric, parallel-strand G-quadruplex to form higher-order structures. Although most of these 256 variants existed primarily as monomers under the conditions of our screen, ∼10% formed dimers or tetramers. These structures could form in a wide range of monovalent and divalent metal ions, and folding was highly cooperative in both KCl and MgCl2. As was previously shown for G-quadruplexes that bind GTP and promote peroxidase reactions, G-quadruplexes that form dimers and tetramers have distinct sequence requirements. Some mutants could also form heteromultimers, and a second screen was performed to characterize the sequence requirements of these structures. Taken together, these experiments provide new insights into the sequence requirements and structures of both homomultimeric and heteromultimeric G-quadruplexes.

A Thermophilic Tetramolecular G‐Quadruplex/Hemin DNAzyme

“…The E a of ABTS oxidation using AG5A as pre‐catalyst was comparable to the E a values of CG5C and TG5T (25.90, 25.33, and 28.37 kJ mol −1 , respectively; Supporting Information, Figure S8), implying that these three pre‐catalysts provide comparable G‐tetrad interaction interface for hemin . However, the activation energy of the oxidation performed with G5 was significantly higher ( E a =43.60 kJ mol −1 ), which might result from the formation of higher‐order G‐quadruplex structures (also termed quadruplex multimerization) through end‐to‐end stacking as demonstrated previously by NMR and polyacrylamide gel electrophoresis (PAGE) analyses . The PAGE analysis showed similar result (Supporting Information, Figure S9), implying that the quadruplex multimerization could prevent proper hemin binding.…”

Structure and Function of Multimeric G-quadruplexes

“…Higher-order GQs which combine these two modes of multimerization have also been described [18,42,[58][59][60][61]. An illustrative example is a GQ structure assembled from eight d(TGGGGT) strands ( Figure 4C).…”

“…On the other hand, this concentration is orders of magnitude higher than that required for 2 of 20 efficient GQ multimerization. For example, in a recent study we identified GQs with dissociation constants of dimer formation as low as 35 nM [18]. The hypothesis that GQs form multimeric structures in cells is also compelling when the myriad evolutionary and functional advantages of this mechanism are considered [19][20][21][22].…”

A Comparative Study on High Selectivities of Human Telomeric Dimeric G‐Quadruplexes by Dimeric G‐Quadruplex Binders

“…[27][28][29][30] Then, compound 3b was incubated with am ixture of G1 and G2T1, and ac ompetition assay of gel electrophoresis was carriedo ut to determinei ts preference towards G2T1 overG 1. This resulted in an ew band that corresponded to ac omplex of G2T1 with compound 3b (G2T1+ +3b).T his band became more intense with increased concentration of compound 3b,w hereas no new bands were observed for the complex of G1 with compound 3b (lanes [6][7][8][9]. Clearly,f ew free antiparallel G2T1 structures were observeda ta3:1c ompound/G2T1 ratio.…”

“…Recently, many studies have reported that about 150-300 nt singlestranded overhang of telomeric DNA has the potentialt of old into multimeric telomeric G-quadruplexesw ith several consecutive G-quadruplex units that are linked by TTAs pacers. [6][7][8][9][10] Moreover,m ost multimeric G-quadruplexes were found in telomeric DNA and RNA regions as well as r(GGGGCC) n RNA re-peats,w hich are relevant in amyotrophic laterals clerosis. [11][12][13][14][15] For these reasons, it is very significant to design small molecules that selectively bind and stabilize multimeric G-quadruplexest owardst he development of potential anticancer agents.…”