Quadruplex polymorphism

Telomeric repeats from other organisms are also prone to quadruplex polymorphism. The Tetrahymena TG4T2G4T telomeric sequence, for example, may adopt several conformations. This sequence forms two novel G-quadruplex structures in Na -containing solution. In the first structure (head-to-head), the two loops are at one end of the G-tetrad core in the second structure (head-to-tail), the two loops are located on opposite ends of the G-tetrad core. In contrast to the human telomere sequence, the proportions of the two forms are similar for a wide range of temperatures their unfolding rates are also similar, with an activation enthalpy of 37 kcal mol . The (G4T4) sequence may also interconvert between parallel and antiparallel structures. 

Abstract Protoberberine alkaloids and related compounds represent an important class of molecules and have attracted recent attention for their various pharmacological activities. This chapter deals with the physicochemical properties of several isoquinoline alkaloids (berberine, palmatine and coralyne) and many of their derivatives under various environmental conditions. The interaction of these compounds with polymorphic DNA structures (B-form, Z-form, H -form, protonated form, triple helical form and quadruplex form) and polymorphic RNA structures (A-form, protonated form, triple helical form and quadruplex form) reported by several research groups, employing various analytical techniques such as spectrophotometry, spectrofluorimetry, circular dichro-ism, NMR spectroscopy, viscometry as well as molecular modelling and thermodynamic analysis to elucidate their mode and mechanism of action for structure-activity relationships, are also presented. 

Intramolecular quadruplexes are often referred to as G4 DNA. Four guanine blocks must be present on the same oligonucleotide sequence and folding of this oligonucleotide into a quadruplex will create three loops. As discussed before, intramolecular quadruplexes are very polymorphic a single sequence may adopt distinct conformations, which will complicate kinetic and thermodynamic analyses. 

G-quadruplex structures are polymorphic regarding the G-tetrad core and the loops. Recent G-quadruplex structures have been reported to contain a variety of new structural elements, as opposed to simpler structures that were reported or proposed a decade ago. This Chapter first describes and classifies the core and loop elements in G-quadruplexes, then examines several examples of recently reported structures. 

G-quadruplex architectures can contain a large variety of G-tetrad core and loop elements. This structural polymorphism depends strongly on sequences and experimental conditions, such as the nature of cations. Some general rules for G-quadruplex folding have emerged, such as the robustness of the... 

The possibility of cation-induced changes in G-quadruplex structure has formed the basis for the hypothesis that DNA G-quadruplexes might function as molecular switches in vAo. In this section we review experiments related to reports of cation-driven conformational changes by G-quadruplexes. While this proposal is certainly related to the cation-dependent polymorphisms described in Section 4.6, the results presented in this section are more focused on G-quadruplex sequences and transitions that have been proposed as possible cation-dependent molecular switches, particularly those sequences derived from telomere DNA sequences. 

Dai J, Carver M, Yang D (2008) Polymorphism of human telomeric quadruplex structures. Biochimie 90 1172-1183... 

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