Chiral introduction of positive charges to PNA for double-duplex invasion to versatile sequences.
Invasion of two PNA strands to double-stranded DNA is one of the most promising methods to recognize a predetermined site in double-stranded DNA (PNA = peptide nucleic acid). In order to facilitate this 'double-duplex invasion', a new type of PNA was prepared by using chiral PNA monomers in which a nucleobase was bound to the alpha-nitrogen of N-(2-aminoethyl)-d-lysine. These positively charged monomer units, introduced to defined positions in Nielsen's PNAs (poly[N-(2-aminoethyl)glycine] derivatives), promoted the invasion without impairing mismatch-recognizing activity. When pseudo-complementary nucleobases 2,6-diaminopurine and 2-thiouracil were bound to N-(2-aminoethyl)-d-lysine, the invasion successfully occurred even at highly G-C-rich regions [e.g. (G/C)7(A/T)3 and (G/C)8(A/T)2] which were otherwise hardly targeted. Thus, the scope of sequences available as the target site has been greatly expanded. In contrast with the promotion by the chiral PNA monomers derived from N-(2-aminoethyl)-d-lysine, their l-isomers hardly invaded, showing crucial importance of the d-chirality. The promotion of double-duplex invasion by the chiral (d) PNA monomer units was ascribed to both destabilization of PNA/PNA duplex and stabilization of PNA/DNA duplexes.
Ishizuka
Takumi
T
Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, 153-8904 Japan.
Yoshida
Junya
J
Yamamoto
Yoji
Y
Sumaoka
Jun
J
Tedeschi
Tullia
T
Corradini
Roberto
R
Sforza
Stefano
S
Komiyama
Makoto
M
D015075:2-Aminopurine / Q000031:analogs & derivatives / Q000737:chemistry; D020856:AT Rich Sequence; D020137:Base Pair Mismatch; D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D020862:GC Rich Sequence; D020135:Peptide Nucleic Acids / Q000737:chemistry*; D055672:Static Electricity; D013237:Stereoisomerism; D013889:Thiouracil / Q000737:chemistry
D020135:Peptide Nucleic Acids; D015075:2-Aminopurine; C007300:2,6-diaminopurine; D013889:Thiouracil; D004247:DNA