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Enzymatic Construction of Artificial Base Pairs: The Effect of Metal Shielding
Author(s) -
Flamme Marie,
LeviAcobas Fabienne,
Hensel Susanne,
Naskar Shuvankar,
Röthlisberger Pascal,
Sarac Ivo,
Gasser Gilles,
Müller Jens,
Hollenstein Marcel
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202000402
Subject(s) - base pair , nucleobase , chemistry , nucleic acid , combinatorial chemistry , metal , nucleotide , nucleoside , steric effects , dna , base metal , stereochemistry , biochemistry , materials science , organic chemistry , welding , metallurgy , gene
Th formation of metal base pairs is a versatile method for the introduction of metal cations into nucleic acids that has been used in numerous applications including the construction of metal nanowires, development of energy, charge‐transfer devices and expansion of the genetic alphabet. As an alternative, enzymatic construction of metal base pairs is an alluring strategy that grants access to longer sequences and offers the possibility of using such unnatural base pairs (UBPs) in SELEX experiments for the identification of functional nucleic acids. This method remains rather underexplored, and a better understanding of the key parameters in the design of efficient nucleotides is required. We have investigated the effect of methylation of the imidazole nucleoside ( dIm n Me TP ) on the efficiency of the enzymatic construction of metal base pairs. The presence of methyl substituents on dImTP facilitates the polymerase‐driven formation of dIm 4Me −Ag I − dIm and dIm 2Me TP −Cr III − dIm base pairs. Steric factors rather than the basicity of the imidazole nucleobase appear to govern the enzymatic formation of such metal base pairs. We also demonstrate the compatibility of other metal cations rarely considered in the construction of artificial metal bases by enzymatic DNA synthesis under both primer extension reaction and PCR conditions. These findings open up new directions for the design of nucleotide analogues for the development of metal base pairs.