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

This paper describes chemical synthesis of prolyl PNAs which are a class of conformationally constrained chiral PNA analogues. The monomers are derive d 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 a nd in the interior to generate chiral PNAs. The complementation studies wit h DNA employing temperature dependent UV spectroscopy indicated that the ch iral modifications in PNA:DNA duplexes imparted both stability and orientat ional preferences. CD spectral studies of chiral PNA:DNA duplexes suggest t hat the D-trans antiparallel duplexes have the B-DNA conformation while L-t rans PNA:DNA duplexes show departure from B-DNA geometry. Thus, inclusion o f even a single backbone constrained distended chiral monomeric unit such a s 4-aminoproline into an achiral PNA chain either at the N-terminus or in t he 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 enhanc es the thermal stability of duplexes. (C) 1998 Elsevier Science Ltd. All ri ghts reserved.