Chiral analogues of peptide nucleic acids: Synthesis of 4-aminoprolyl nucleic acids and DNA complementation studies using UV/CD spectroscopy

被引:48
作者
Gangamani, BP [1 ]
Kumar, VA [1 ]
Ganesh, KN [1 ]
机构
[1] Natl Chem Lab, Div Organ Chem Synth, Pune 411008, Maharashtra, India
关键词
peptide nucleic acids; chiral analogues; electronic spectra; circular dichroism;
D O I
10.1016/S0040-4020(98)01024-2
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
This paper describes chemical synthesis of prolyl PNAs which are a class of conformationally constrained chiral PNA analogues. The monomers are derived from bridging the ethylenediamine and glycine components of the same unit which leads to PNA based on 4-aminoproline backbone with chirality at C-4 and C-2. The modified monomers corresponding to D-trans and L-trans prolyl-T have been incorporated into standard PNA chains, both at the N-terminus and in the interior to generate chiral PNAs. The complementation studies with DNA employing temperature dependent UV spectroscopy indicated that the chiral modifications in PNA:DNA duplexes imparted both stability and orientational preferences. CD spectral studies of chiral PNA:DNA duplexes suggest that the D-trans antiparallel duplexes have the B-DNA conformation while L-trans PNA:DNA duplexes show departure from B-DNA geometry. Thus, inclusion of even a single backbone constrained distended chiral monomeric unit such as 4-aminoproline into an achiral PNA chain either at the N-terminus or in the interior. leads to stabilization of the PNA:DNA hybrid. The linking of a polycation such as spermine at the C-terminus of chiral PNA further enhances the thermal stability of duplexes. (C) 1998 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:177 / 192
页数:16
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