The 2‐Amino Group of 8‐Aza‐7‐deaza‐7‐bromopurine‐2,6‐diamine and Purine‐2,6‐diamine as Stabilizer for the Adenine–Thymine Base Pair in Heterochiral DNA with Strands in Anomeric Configuration

Abstract

Stabilization of DNA is beneficial for many applications in the fields of DNA therapeutics, diagnostics, and materials science. Now, this phenomenon is studied on heterochiral DNA, an autonomous DNA recognition system with complementary strands in α‐D and β‐D configuration showing parallel strand orientation. The 12‐mer heterochiral duplexes were constructed from anomeric (α/β‐D) oligonucleotide single‐strands. Purine‐2,6‐diamine and 8‐aza‐7‐deaza‐7‐bromopurine‐2,6‐diamine 2′‐deoxyribonucleosides having the capability to form tridentate base pairs with dT were used to strengthen the stability of the dA–dT base pair. Tm data and thermodynamic values obtained from UV melting profiles indicated that the 8‐aza‐7‐deaza 2′‐deoxyribonucleoside decorated with a bromo substituent is so far the most efficient stabilizer for heterochiral DNA. Compared with that, the stabilizing effect of the purine‐2,6‐diamine 2′‐deoxyribonucleoside is low. Global changes of helix structures were identified by circular dichroism (CD) spectra during melting.

Anomeric DNA: Functionalization of α‐d Anomers of 7‐Deaza‐2′‐deoxyadenosine and 2′‐Deoxyuridine with Clickable Side Chains and Click Adducts in Homochiral and Heterochiral Double Helices

“…Various factors contribute to the shape of the CD‐spectra: i) the conformation of the monomers which can be syn or anti , ii) the conformation of the sugar residues ( N vs. S ), iii) the hydrogen‐bonding network formed between nucleobases, iv) stacking interactions between nucleobases or base pairs and v) the helicity of the duplex (+ or −). Previous CD experiments have shown that CD spectra of α‐anomeric single strands display spectra with mirror‐like Cotton effects with respect to the β‐strand [1,2,3] . Complete mirror images are not expected as diastereoisomers are compared and not enantiomeric molecules with strands in d ‐ and l ‐configuration.…”

“…Previous CD experiments have shown that CD spectra of α‐anomeric single strands display spectra with mirror‐like Cotton effects with respect to the β‐strand. [ 1 , 2 , 3 ] Complete mirror images are not expected as diastereoisomers are compared and not enantiomeric molecules with strands in d ‐ and l ‐configuration. The phenomenon has been already discussed for nonfunctionalized α‐ d hexamer oligonucleotide duplexes with all‐purine or all‐pyrimidine bases in either the α‐ or the β‐strand.…”

“…Anomeric DNA is formed when one strand of a duplex is in the α‐ d and the other in the β‐ d ‐configuration [1,2] . When DNA is constructed from two strands in the α‐ d configuration, homochiral α/α‐DNA is generated; the anomeric counterpart to canonical DNA.…”

“…Anomeric DNA is formed when one strand of a duplex is in the α‐ d and the other in the β‐ d ‐configuration. [ 1 , 2 ] When DNA is constructed from two strands in the α‐ d configuration, homochiral α/α‐DNA is generated; the anomeric counterpart to canonical DNA. The strand orientation in heterochiral α/β‐DNA is parallel, whereas homochiral α/α‐DNA displays an antiparallel alignment.…”

DNA Strand Displacement with Base Pair Stabilizers: Purine‐2,6‐Diamine and 8‐Aza‐7‐Bromo‐7‐Deazapurine‐2,6‐Diamine Oligonucleotides Invade Canonical DNA and New Fluorescent Pyrene Click Sensors Monitor the Reaction

“…Nucleoside 2 found widespread application as efficient DNA stabilizer without disturbing the DNA double helical structure [8h,10] . The stabilizing properties of 1 and 2 were used to strengthen homochiral and heterochiral DNA and to harmonize the stability of the dA‐dT and dG‐dC base pair [8h,10] . The stabilizers 1 and 2 have been already incorporated in DNA by solid‐phase synthesis employing phosphoramidite chemistry [8h,10,12] .…”