Abstract:
Peptide nucleic acid (PNA) is a prominent artificial nucleic acid mimetic and modifications at the γ-position of the peptidic backbone are known to further enhance the desirable properties of PNA in terms of duplex stability. Here, we leveraged a propargyl ether modification at this position for late stage functionalization of PNA to obtain positively charged (cationic amino and guanidinium groups), negatively charged (anionic carboxylate and alkyl phosphonate groups) and neutral (PEG) PNAs to assess the impact of these charges on DNA : PNA and PNA : PNA duplex formation. Thermal stability analysis findings concurred with prior studies showing PNA : DNA duplexes are moderately more stable with cationic PNAs than anionic PNAs at physiological salt concentrations. We show that this effect is derived predominantly from differences in the association kinetics. For PNA : PNA duplexes, anionic PNAs were found to form the most stable duplexes, more stable than neutral PNA : PNA duplexes.
摘要:
肽核酸(PNA)是突出的人工核酸模拟物,并且已知在肽主链的γ-位置处的修饰在双链体稳定性方面进一步增强PNA的期望性质。这里,我们在这个位置利用炔丙基醚修饰进行PNA的后期官能化,以获得带正电荷的(阳离子氨基和胍基),带负电荷(阴离子羧酸盐和烷基膦酸基团)和中性(PEG)PNA以评估这些电荷对DNA:PNA和PNA:PNA双链体形成的影响。热稳定性分析发现与先前的研究一致,表明在生理盐浓度下,PNA:DNA双链体对阳离子PNA比阴离子PNA适度更稳定。我们表明,这种效应主要来自缔合动力学的差异。对于PNA:PNA双链体,发现阴离子PNA形成最稳定的双链体,比中性PNA更稳定:PNA双链体。