Affinity and Selectivity of C2-and C5-Substituted "Chiral-Box" PNA in Solution and on Microarrays

被引:20
作者
Manicardi, Alex [1 ]
Calabretta, Alessandro [1 ]
Bencivenni, Mariangela [1 ]
Tedeschi, Tullia [1 ]
Sforza, Stefano [1 ]
Corradini, Roberto [1 ]
Marchelli, Rosangela [1 ]
机构
[1] Univ Parma, Dipartimento Chim Organ & Ind, I-43100 Parma, Italy
关键词
PNA; DNA recognition; chiral monomers; single nucleotide polymorphisms; microarrays; PEPTIDE NUCLEIC-ACID; SOLID-PHASE SYNTHESIS; SEQUENCE B-DNA; STRAND INVASION; CYSTIC-FIBROSIS; POINT MUTATION; LYSINE; BACKBONE; BINDING; HYBRIDIZATION;
D O I
10.1002/chir.20865
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Two peptide nucleic acids (PNAs) containing three adjacent modified chiral monomers (chiral box) were synthesized. The chiral monomers contained either a C2- or a C5-modified backbone, synthesized starting from D-and L-arginine, respectively (2D- and 5L-PNA). The C2-modified chiral PNA was synthesized using a submonomeric strategy to avoid epimerization during solid-phase synthesis, whereas for the C5-derivative, the monomers were first obtained and then used in solid-phase synthesis. The melting temperature of these PNA duplexes formed with the full-match or with single-mismatch DNA were measured both by UV and by CD spectroscopy and compared with the unmodified PNA. The 5L-chiral-box-PNA showed the highest T-m with full-match DNA, whereas the 2D-chiral-box-PNA showed the highest sequence selectivity. The PNA were spotted on microarray slides and then hybridized with Cy5-labeled full match and mismatched oligonucleotides. The results obtained showed a signal intensity in the order achiral > 2D-chiral box > 5L-chiral box, whereas the full-match/mismatch selectivity was higher for the 2D chiral box PNA. Chirality 22:E161-E172, 2010. (c) 2010 Wiley-Liss, Inc.
引用
收藏
页码:E161 / E172
页数:12
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