Reversible manipulation of the G-quadruplex structures and enzymatic reactions through supramolecular host–guest interactions

Abstract

Supramolecular chemistry addresses intermolecular forces and consequently promises great flexibility and precision. Biological systems are often the inspirations for supramolecular research. The G-quadruplex (G4) belongs to one of the most important secondary structures in nucleic acids. Until recently, the supramolecular manipulation of the G4 has not been reported. The present study is the first to disclose a supramolecular switch for the reversible control of human telomere G4s. Moreover, this supramolecular switch has been successfully used to manipulate an enzymatic reaction. Using various methods, we show that cucurbit[7]uril preferably locks and encapsulates the positively charged piperidines of Razo through supramolecular interactions. They can switch the conformations of the DNA inhibitor between a flexible state and the rigid G4 and are therefore responsible for the reversible control of the thrombin activity. Thus, our findings open a promising route and exhibit potential applications in future studies of chemical biology.

Reversible Photocontrol of DNA Melting by Visible‐Light‐Responsive F4‐Coordinated Azobenzene Compounds

“…Analysis of the CD data in the spectral range of <300 nm cannot be easily described owing to the superimposed signals of the intrinsic duplex/quadruplex chirality with the ICD signals of the molecular photoswitches. In striking contrast with previously reported symmetric dicharged azobenzene‐based G4 binders, our photochromes were not able to induce a conformational conversion of Tel‐22 . These results seem to be strictly connected to the nature of the substituents attached to the azobenzene scaffold.…”

“…These results seem to be strictly connected to the nature of the substituents attached to the azobenzene scaffold. Indeed, supramolecular modulation of the G4 structure was made by using azo compounds that featured either positively charged piperidine units or N ‐trimethylethan‐1‐aminium moieties that were connected through short methylene bridges, which perfectly matched the terminal G‐quartets . In our case, both the asymmetric structure of mono‐Azo4F and the higher number of charges along the polyamine backbone coupled with longer methylene spacers of bis‐Azo4F may preclude their optimal end‐stacking ability, which would inhibit the reversible regulation of the G‐rich sequence.…”

Applications of Cucurbit[n]urils (n=7 or 8) in Pharmaceutical Sciences and Complexation of Biomolecules

“…(b) Superposition of the two insulins illustrates the strong homology between 1a and 1b with clear divergence at the N-terminus of the B-chain. [70] In this work, a synthetic molecule Razo was used as a key to manipulate human telomere G-quadruplex (G4), one of the most important secondary structures in nucleic acids, which changed from a flexible strand to rigid G4. Reprinted with permission from Ref.…”

“…[59]. [70] Besides enzymes and proteins, CB[n] (n = 7 or 8) can also influence DNA. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 Furthermore, the biological activities of guest peptides or protein may be modulated upon their binding with CB [7] or CB [8].…”

Host–Guest Tethered DNA Transducer: ATP Fueled Release of a Protein Inhibitor from Cucurbit[7]uril

“…19–26 However, achieving guest release from CB7 (or other CB) complexes using relevant biomolecule triggers remains a formidable challenge. The current state-of-the-art is to: a) use covalent enzymatic transformations that can catalyze the formation of a product which is a strong CB7 binder 27,28 or b) use biomolecules that have been identified to have the appropriate chemical structure to bind tightly into the CB cavity.…”