The interactions between nucleic acids and polyamines

Polyamine‐Functionalized 2′‐Amino‐LNA in Oligonucleotides: Facile Synthesis of New Monomers and High‐Affinity Binding towards ssDNA and dsDNA

“…This is likely caused by the higher buffer capacity provided by the six aminog roups of ON8,w hich likely are fully protonated at the experimental pH value of 7.0. [45] The same relationb etween duplex stabilization and salt concentration was observed for the two reference strands ON1 and ON2.T his was expected, as the pK a value of the 2'-amino group in 2'-amino-LNA-Th as been reported to be 6.17. [46] Binding specificity was assessed for ON3, ON4 and ON5 in comparison with ON1 with the nucleobase complementary to the site of modification on the opposite strandsb eing varied from adenosine to guanine, cytosine or thymine/uracil centrally (Table S3 in the SupportingI nformation).…”

Determination of microscopic acid?base parameters from NMR?pH titrations

“…Protonation fractions as a function of pH have been determined for ethylenediamine, trien 8, and tetren 9 by 1 H [106] and 13 C NMR [152], for 3,2,3-tet and 3,3,3-tet (for nomenclature, see ref. [151]) by 13 C NMR [155], for spermine (10) and spermidine (11) by 1 H [156] and 13 C NMR [153,154], for thermospermine by 15 N NMR [157] and for the neuroactive wasp toxin philanthotoxin-343 by 1 H and 13 C NMR titration [158]. Microconstants have been determined by NMR titration for N-(2-mercaptoethyl)-1,3-diaminopropane [159], tetren [27], spermine, spermidine, and homologues [154,160].…”

The regiochemical distribution of positive charges along cholesterol polyamine carbamates plays significant roles in modulating DNA binding affinity and lipofection

“…The charge distribution is clearly important for molecular recognition, but also the hydrophobic polymethylene backbone confers structural flexibility and the possibility of important secondary binding interactions. There are multiple parallel protonation pathways for the basic centres of the partially protonated species which may account for many of the biochemical functions of these molecules [16]. DNA condensation is dependent upon three characteristic properties of natural or synthetic polyamines: firstly, the number of positive charges which therefore influence the local ionic strength [17,18]; secondly, the regiochemical distribution of these charges whose p K a s are intimately dependent upon their cooperativity [16,18,19]; thirdly, the local salt concentration [4,18].…”

“…There are multiple parallel protonation pathways for the basic centres of the partially protonated species which may account for many of the biochemical functions of these molecules [16]. DNA condensation is dependent upon three characteristic properties of natural or synthetic polyamines: firstly, the number of positive charges which therefore influence the local ionic strength [17,18]; secondly, the regiochemical distribution of these charges whose p K a s are intimately dependent upon their cooperativity [16,18,19]; thirdly, the local salt concentration [4,18]. Although Wilson and Bloomfield [4] predict, using Manning's polyelectrolyte theory [20], that condensation will occur when the polyamine:DNA charge ratio approaches 1:1 (when typically ∼90% of the DNA polyanionic charge has been neutralised), in practice, the off‐rate of binding of simple polyamines is so large as to require a several‐fold charge excess of polyamine to DNA (polyammonium ions to phosphate) in order to effect efficient condensation of DNA.…”