The influence of G-quadruplex structure on DNA-based asymmetric catalysis using the G-quadruplex-bound cationic porphyrin TMPyP4·Cu

Abstract

The DNA G-quadruplex-binding porphyrin TMPyP4·Cu was found to form efficient hybrid catalysts for DNA-based asymmetric catalysis when bound to DNA G-quadruplexes. Nucleobase substitution experiments using human telomere-derived G-quadruplex sequences suggest binding of the porphyrin on the 3'-face.

Enantioselectively-Catalyzed Reactions with (E)-2-Alkenoyl-pyridines, TheirN-Oxides, and the Corresponding Chalcones

“…With KCl (2R,3R)-78 is obtained in 44% ee, with NaCl the enantioselectivity is inverted and (2S,3S)-78 is obtained with 53% ee, a result that implies a conformational change of the G-quadruplex. 67 This Na + /K + switch of enantioselectivity in G4 catalysis has been recently observed in the D.A. reaction between (E)-1-(1-phenyl-1H-imidazol-2-yl)but-2-en-1-one (already mentioned in Scheme 19) and cyclopentadiene and this unusual change in stereocontrol, to our opinion, is a virgin field to be explored.…”

“…Colored spots are the quadruplex guanines, and black spots are nucleobases overlooking (or located on the loops connecting) the guanine tetrads. 67,68 An interesting result was obtained substituting KCl with NaCl in the buffer (Table 22, entry 2 vs 3). With [XXXVIIIa/ Cu(NO 3 ) 2 ] enantioselectivity drops from 58 to 10% ee, but the result is even more dramatic when the reaction is catalyzed with only Cu(NO 3 ) 2 .…”

“…67 This is the end of a chapter in which a topic, once rather unusual dealing with chiral enantioselective catalysts, but that is the subject of a specific review, 70 1 (or 2). Perhaps not all the catalysts will give results comparable to those of the more traditional literature, but certainly this new kind of catalysts is "the new entry" in the field.…”

DNA-based hybrid catalysis

“…Hennecke and co-workers developed a hybrid catalyst comprising the copper(II) complex of TMPyP4 and Gquadruplex DNA (Figure 3) [29]. Depending on the sequence of the DNA, up to 68% ee was achieved in the catalyzed enantioselective Diels-Alder reactions.…”

Artificial Metalloenzymes for Asymmetric Catalysis by Creation of Novel Active Sites in Protein and DNA Scaffolds

“…This might be related to the more shallow grooves present in DNA quadruplex structures, that is, catalysis takes place mainly on the surface of the DNA quadruplex structure, which makes the transfer of chirality less efficient. Catalysis could be improved significantly by employing the cationic porphyrin TMPY4⋅Cu as the catalytically active metal complex 63. By optimizing the DNA quadruplex sequence, up to 68 % ee was achieved in the DielsAlder reaction.…”