Role of chirality and optical purity in nucleic acid recognition by PNA and PNA analogs.
Peptide nucleic acids are DNA mimics able to form duplexes with complementary DNA or RNA strands of remarkable affinity and selectivity. Oligopyrimidine PNA can displace one strand of dsDNA by forming PNA(2):DNA triplexes of very high stability. Many PNA analogs have been described in recent years, in particular, chiral PNA analogs. In the present article the results obtained recently using PNA derived from N-aminoethylamino acids 7 are illustrated. In particular, the dependence of optical purity on synthetic methodologies and a rationale for the observed effects of chirality on DNA binding ability is proposed. Chirality as a tool for improving sequence selectivity is also described. PNA analogs derived from D- or L-ornithine 8 were also found to be subjected to epimerization during solid phase synthesis. Modification of the coupling conditions or the use of a submonomeric strategy greatly reduced epimerization. The optically pure oligothymine PNAs 8 were found to bind to RNA by forming triplexes of unusual CD spectra. The melting curves of these adducts presented two transitions, suggesting a conformational change followed by melting at high temperature.
Dipartimento di Chimica Organica e Industriale Università di Parma-Parco Area delle Scienze, Parma, Italy.
Stefano
S
Sforza
Gianni
G
Galaverna
Arnaldo
A
Dossena
Roberto
R
Corradini
Rosangela
R
Marchelli
D002621:Chemistry / Q000379:methods; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D008401:Gas Chromatography-Mass Spectrometry; D008956:Models, Chemical; D009696:Nucleic Acids / Q000737:chemistry*; D020135:Peptide Nucleic Acids / Q000737:chemistry*; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D013053:Spectrophotometry; D013237:Stereoisomerism; D013696:Temperature; D013816:Thermodynamics; D014466:Ultraviolet Rays
D009696:Nucleic Acids; D020135:Peptide Nucleic Acids; D012313:RNA; D004247:DNA