Constrained Flexibility in Pna: Dna Binding Studies With Bridged Aminopropylglycyl Pna

Abstract

Introduction of methylene bridges in aegPNA and apgPNA molecules give rise to cyclic five and six membered ring structures. Synthesis of a new six membered cyclic PNA monomer, aminopipecolyl PNA (pipPNA) is reported. Incorporation of pipPNA into PNA oligomers and comparative binding with target DNA sequences is studied.

trans-5-Aminopipecolyl-aegPNA Chimera: Design, Synthesis, and Study of Binding Preferences with DNA/RNA in Duplex/Triplex Mode

“…1 H NMR CDCl3 δ: 7.35(s, 5H), 5.2 (d, 2H), 5-4.75(m, 1H), 4.7-4.3 (m, H6), 3.7 (m, 3H), 3.1 (m, 3H), 2.5-1.4 (m, 5H). 13 (2S,5R)-5-Azido-N-1 (Benzyloxycarbonyl)pipecolic Acid Methyl Ester 3. To the compound 2 (0.74 g, 1.99 mmol) in dry DMF was added NaN3 (0.76 g, 11.6 mmol).…”

“…These involved introduction of a methylene bridge between the R′ carbon atom of the glycyl moiety and the β/γ carbon atom of the aminoethyl/aminopropyl segment of the parent aeg/apgPNA to generate five-/six-membered pyrrolidine/piperidine rings. The comparative UV-T m studies after incorporation of these two modifications in a triplex forming aegPNAT 10 sequence showed that both (2S,4R) five- 12 and (2S,4S) six-membered 13 trans ring conformations caused detrimental effects on the stability of PNA 2 :DNA and thus were incapable of adopting the structural bias required for PNA 2 :DNA triplex formation. The primary knowledge of the stability of trans conformations in six-membered rings suggested that a trans-5-aminopipecolyl monomer (Figure 1,V) could be a better choice because of the stable, favored diequatorial disposition of the backbone.…”

“…14 In this note, we present our results on the synthesis and hybridization properties of the designed trans-(2S,5R)-5-aminopipecolyl thyminyl PNA monomer, its incorporation into triplex-and duplex-forming oligomers, and their DNA and RNA binding studies in comparison with the trans-4-aminopipecolyl PNA analogue reported earlier. 13 Synthesis of 5-Aminopipecolyl PNA Monomer. The chiral pipecolyl PNA thymine monomer trans-(5R)-(N-Boc-amino)-N-(thymin-1-ylacetyl)-(2S)-pipecolic acid 7 was synthesized from cis-N-benzyloxycarbonyl-(5S)hydroxy-(2S)-pipecolic acid methyl ester 1, which in turn was synthesized from L-glutamic acid 15 (Scheme 1).…”

“…12,19 The mixed base oligomers 17-19 were synthesized to study the effect of modification in duplex binding mode. The synthesis of PNA oligomers comprising standard aegPNA monomers, 4-aminopipecolyl PNA monomer, 13 and 7 was carried out using standard solid-phase synthesis protocols. 20 The oligomers after the synthesis were cleaved from the support using trifluoroacetic acid-trifluoromethanesulfonic acid 21 to yield the PNA oligomers carrying β-alanine at their carboxy termini (Table 1 and Table 2).…”

Synthesis of Free and Nα‐Fmoc‐/Nγ‐Boc‐Protected (2S,4S)‐ and (2S,4R)‐4‐Aminopipecolic Acids

“…4-Aminopipecolic acid has been found in the leaves of Strophantus scandens (Apocinaceae), [15Ϫ17] its stereochemistry not being assigned with certainty, and (2S,4S)-4-acetylamino pipecolic acid has been isolated from the leaves of Calliandra haematocephala (Leguminosae). [18] This amino acid moiety has been incorporated into different synthetic biologically active compounds such as cyclic peptides, [19Ϫ21] oligomers [22] and small molecules.…”