A "Retro-Inverso" PNA: Structural implications for DNA and RNA binding

A.H. Krotz; S. Larsen; Ole Buchardt; M. Eriksson; Peter Eigil Nielsen

doi:10.1016/s0968-0896(98)00152-7

A "Retro-Inverso" PNA: Structural implications for DNA and RNA binding

A.H. Krotz, S. Larsen, Ole Buchardt, M. Eriksson, Peter Eigil Nielsen

Transcription, RNA, and Gene Medicine Program

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

15 Citationer (Scopus)

Abstract

Nucleic acid, hybridization, antisense, peptide nucleic acid

Originalsprog	Engelsk
Tidsskrift	Bioorganic & Medicinal Chemistry
Vol/bind	6
Udgave nummer	11
Sider (fra-til)	1983-1992
ISSN	0968-0896
DOI	https://doi.org/10.1016/s0968-0896(98)00152-7
Status	Udgivet - 1998

Adgang til dokumentet

10.1016/s0968-0896(98)00152-7

Citationsformater

@article{2f2e387074c111dbbee902004c4f4f50,

title = "A {"}Retro-Inverso{"} PNA: Structural implications for DNA and RNA binding",

abstract = "'Retro-inverso' peptide nucleic acid (PNA) monomers of thymine (T*: N-(amidomethyl)-N-(N1-thyminyl-acetyl)-beta-alanyl) (and adenine) have been prepared and introduced in PNA oligomers. A homo 'retro-inverso' T*8 PNA was found not to hybridize to a complementary DNA or RNA oligonucleotide, whereas introduction of one retro-inverso thymine unit into the middle of a normal PNA 15-mer resulted in a c.a. 8 degrees C destabilization of the complex of this oligomer with a complementary DNA or RNA oligomer. In an effort to compensate for the structural nucleobase 'phase-shift' caused by the T* monomer by also introducing a beta-alanine monomer it is concluded that the effect of the T* backbone is -7 degrees C when hybridizing to DNA and -4.5 degrees C when hybridizing to RNA. Nonetheless, the T* unit shows good sequence discrimination comparable to that of normal PNA. Molecular dynamics simulations indicate an unfavourable conformation of the backbone amide carbonyl group resulting in reduced interaction with the aqueous medium and an 'electrostatic clash' with the carbonyl of the nucleobase linker. These results show that a simple inversion of an amide bond in the PNA backbone has a dramatic, and hardly predictable, effect on the DNA mimicking properties of the oligomer.",

author = "A.H. Krotz and S. Larsen and Ole Buchardt and M. Eriksson and Nielsen, {Peter Eigil}",

year = "1998",

doi = "10.1016/s0968-0896(98)00152-7",

language = "English",

volume = "6",

pages = "1983--1992",

journal = "Bioorganic & Medicinal Chemistry",

issn = "0968-0896",

publisher = "Pergamon Press",

number = "11",

}

TY - JOUR

T1 - A "Retro-Inverso" PNA: Structural implications for DNA and RNA binding

AU - Krotz, A.H.

AU - Larsen, S.

AU - Buchardt, Ole

AU - Eriksson, M.

AU - Nielsen, Peter Eigil

PY - 1998

Y1 - 1998

N2 - 'Retro-inverso' peptide nucleic acid (PNA) monomers of thymine (T*: N-(amidomethyl)-N-(N1-thyminyl-acetyl)-beta-alanyl) (and adenine) have been prepared and introduced in PNA oligomers. A homo 'retro-inverso' T*8 PNA was found not to hybridize to a complementary DNA or RNA oligonucleotide, whereas introduction of one retro-inverso thymine unit into the middle of a normal PNA 15-mer resulted in a c.a. 8 degrees C destabilization of the complex of this oligomer with a complementary DNA or RNA oligomer. In an effort to compensate for the structural nucleobase 'phase-shift' caused by the T* monomer by also introducing a beta-alanine monomer it is concluded that the effect of the T* backbone is -7 degrees C when hybridizing to DNA and -4.5 degrees C when hybridizing to RNA. Nonetheless, the T* unit shows good sequence discrimination comparable to that of normal PNA. Molecular dynamics simulations indicate an unfavourable conformation of the backbone amide carbonyl group resulting in reduced interaction with the aqueous medium and an 'electrostatic clash' with the carbonyl of the nucleobase linker. These results show that a simple inversion of an amide bond in the PNA backbone has a dramatic, and hardly predictable, effect on the DNA mimicking properties of the oligomer.

AB - 'Retro-inverso' peptide nucleic acid (PNA) monomers of thymine (T*: N-(amidomethyl)-N-(N1-thyminyl-acetyl)-beta-alanyl) (and adenine) have been prepared and introduced in PNA oligomers. A homo 'retro-inverso' T*8 PNA was found not to hybridize to a complementary DNA or RNA oligonucleotide, whereas introduction of one retro-inverso thymine unit into the middle of a normal PNA 15-mer resulted in a c.a. 8 degrees C destabilization of the complex of this oligomer with a complementary DNA or RNA oligomer. In an effort to compensate for the structural nucleobase 'phase-shift' caused by the T* monomer by also introducing a beta-alanine monomer it is concluded that the effect of the T* backbone is -7 degrees C when hybridizing to DNA and -4.5 degrees C when hybridizing to RNA. Nonetheless, the T* unit shows good sequence discrimination comparable to that of normal PNA. Molecular dynamics simulations indicate an unfavourable conformation of the backbone amide carbonyl group resulting in reduced interaction with the aqueous medium and an 'electrostatic clash' with the carbonyl of the nucleobase linker. These results show that a simple inversion of an amide bond in the PNA backbone has a dramatic, and hardly predictable, effect on the DNA mimicking properties of the oligomer.

U2 - 10.1016/s0968-0896(98)00152-7

DO - 10.1016/s0968-0896(98)00152-7

M3 - Journal article

VL - 6

SP - 1983

EP - 1992

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

SN - 0968-0896

IS - 11

ER -