Pyrrolidinyl peptide nucleic acid with α/β-peptide backbone: A conformationally constrained PNA with unusual hybridization properties

Chotima Vilaivan; Choladda Srisuwannaket; Cheeraporn Ananthanawat; Chaturong Suparpprom; Junji Kawakami; Yoshie Yamaguchi; Yuko Tanaka; Tirayut Vilaivan

doi:10.4161/adna.2.2.16340

Pyrrolidinyl peptide nucleic acid with α/β-peptide backbone: A conformationally constrained PNA with unusual hybridization properties

Artif DNA PNA XNA. 2011 Apr;2(2):50-59. doi: 10.4161/adna.2.2.16340.

Authors

Chotima Vilaivan¹, Choladda Srisuwannaket, Cheeraporn Ananthanawat, Chaturong Suparpprom, Junji Kawakami, Yoshie Yamaguchi, Yuko Tanaka, Tirayut Vilaivan

Affiliation

¹ Organic Synthesis Research Unit; Department of Chemistry; Faculty of Science; Chulalongkorn University; Patumwan, Bangkok, Thailand.

Abstract

We describe herein a new conformationally constrained analog of PNA carrying an alternating α/β amino acid backbone consisting of (2'R,4'R)-nucleobase-subtituted proline and (1S,2S)-2-aminocyclopentanecarboxylic acid (acpcPNA). The acpcPNA has been synthesized and evaluated for DNA, RNA and self-pairing properties by thermal denaturation experiments. It can form antiparallel hybrids with complementary DNA with high affinity and sequence specificity. Unlike other PNA systems, the thermal stability of acpcPNA·DNA hybrid is largely independent of G+C contents, and is generally higher than that of acpcPNA·RNA hybrid with the same sequence. Thermodynamic parameters analysis suggest that the A·T base pairs in the acpcPNA·DNA hybrids are enthalpically stabilized over G·C pairs. The acpcPNA also shows a hitherto unreported behavior, namely the inability to form self-pairing hybrids. These unusual properties should make the new acpcPNA a potentially useful candidate for various applications including microarray probes and antigene agents.