Nucleotide analogues as probes for DNA polymerases

Abstract

Transmission of the genetic information from the parental DNA strand to the offspring is crucial for the survival of any living species. In nature, all DNA synthesis in DNA replication, recombination and repair is catalyzed by DNA polymerases and depends on their ability to select the canonical nucleobase pair from a pool of structurally similar building blocks. Recently, a wealth of valuable new insights into DNA polymerase mechanisms have been gained through application of carefully designed synthetic nucleotides and oligonucleotides in functional enzyme studies. The applied analogues exhibit features that differ in certain aspects from their natural counterparts and, thus, allow investigation of the involvement and efficacy of a chosen particular aspect on the entire complex enzyme mechanism. This review will focus on a depiction of the efforts that have been undertaken towards the development of nucleotide analogues with carefully altered properties. The different approaches will be discussed in the context of the motivation and the problem under investigation.

Structures of DNA Polymerases Caught Processing Size‐Augmented Nucleotide Probes

“…[2] In this context nucleotides with hydrophobic nucleobase isosteres were developed to study the contribution of hydrogen bonding to DNA polymerase selectivity.…”

Recent Progress Toward the Templated Synthesis and Directed Evolution of Sequence-Defined Synthetic Polymers

“…The impetus for much of this work has been to study nucleic acid duplex stability and the function of DNA and RNA polymerases, and has been reviewed recently (Hwang and Romesberg, 2006; Henry and Romesberg, 2003; Hirao, 2006; Jung and Marx, 2005; Kool, 2001). The discovery of novel, polymerase-compatible nucleic acid bases has created interest in synthetic polymers that might contain higher densities of information than DNA or RNA, or ones that may even be used in orthogonal transcription systems.…”

“…In this manner, more than 100 functionalized nucleotides have been incorporated into DNA and RNA, including those containing nucleophilic groups such as amines and thiols, electrophilic groups such as acrylates and aldehydes, proton donors and acceptors such as imidazole, pyridine, and guanidinium groups, and reactive groups such as cyanoborohydride. Many of these efforts are summarized in Figure 2; this area has also been reviewed recently (Jung and Marx, 2005; Porter et al, 1995; Hocek and Fojta, 2008; Krayevsky et al, 1996; Kuwahara et al, 2006; McGall, 2005). …”

“…(A) Nucleic acid bases can be modified at several different positions (labeled X) without abolishing Watson-Crick base pairing or the ability of the resulting nucleotide to be incorporated into an oligonucleotide using a polymerase enzyme (Jung and Marx, 2005; Hocek and Fojta, 2008; Krayevsky et al, 1996; Kuwahara et al, 2006). …”

Hydrogen Bonds and Stacking Interactions on the DNA Structure: A Topological View of Quantum Computing

“…With a function of organic acid, the great DNA action consists into the organization and regulation of the genetic informations, which are simply so-called as genes (Gräslund et al, 2010). Thus, due to the immensity of genes to be taken into account, the DNA composition transformed it into a large olygomer formed by nucleotide subunits (Jung & Marx, 2005), and therefore DNA is considered one of the largest macromolecules ever known. Within the cellular environment, the DNA is organized into some very long structures so-named chromosomes, which are duplicated through the cell division process.…”