Sequence-selective minor groove recognition of a DNA duplex containing synthetic genetic components

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Abstract

The structural basis of minor groove recognition of a DNA duplex containing synthetic genetic information by hairpin pyrrole-imidazole polyamides is described. Hairpin polyamides induce a higher melting stabilization of a DNA duplex containing the unnatural P·Z base-pair when an imidazole unit is aligned with a P nucleotide. An NMR structural study showed that the incorporation of two isolated P·Z pairs enlarges the minor groove and slightly narrows the major groove at the site of this synthetic genetic information, relative to a DNA duplex consisting entirely of Watson-Crick base-pairs. Pyrrole-imidazole polyamides bind to a P·Z-containing DNA duplex to form a stable complex, effectively mimicking a G·C pair. A structural hallmark of minor groove recognition of a P·Z pair by a polyamide is the reduced level of allosteric distortion induced by binding of a polyamide to a DNA duplex. Understanding the molecular determinants that influence minor groove recognition of DNA containing synthetic genetic components provides the basis to further develop unnatural base-pairs for synthetic biology applications.

LanguageEnglish
Pages9555-9563
Number of pages9
JournalJournal of the American Chemical Society
Volume141
Issue number24
Early online date22 May 2019
DOIs
Publication statusPublished - 19 Jun 2019

Fingerprint

Nylons
Polyamides
DNA
Base Pairing
Pyrroles
Z-Form DNA
Synthetic Biology
Freezing
Nucleotides
Melting
Stabilization
Nuclear magnetic resonance
imidazole

Keywords

  • DNA
  • minor groove recognition
  • unnatural base-pairs
  • synthetic biology
  • NMR

Cite this

@article{22092b587baa4d85a615cdf3261b6eca,
title = "Sequence-selective minor groove recognition of a DNA duplex containing synthetic genetic components",
abstract = "The structural basis of minor groove recognition of a DNA duplex containing synthetic genetic information by hairpin pyrrole-imidazole polyamides is described. Hairpin polyamides induce a higher melting stabilization of a DNA duplex containing the unnatural P·Z base-pair when an imidazole unit is aligned with a P nucleotide. An NMR structural study showed that the incorporation of two isolated P·Z pairs enlarges the minor groove and slightly narrows the major groove at the site of this synthetic genetic information, relative to a DNA duplex consisting entirely of Watson-Crick base-pairs. Pyrrole-imidazole polyamides bind to a P·Z-containing DNA duplex to form a stable complex, effectively mimicking a G·C pair. A structural hallmark of minor groove recognition of a P·Z pair by a polyamide is the reduced level of allosteric distortion induced by binding of a polyamide to a DNA duplex. Understanding the molecular determinants that influence minor groove recognition of DNA containing synthetic genetic components provides the basis to further develop unnatural base-pairs for synthetic biology applications.",
keywords = "DNA, minor groove recognition, unnatural base-pairs, synthetic biology, NMR",
author = "Giacomo Padroni and Withers, {Jamie M.} and {Taladriz Sender}, Andrea and Reichenbach, {Linus F.} and Parkinson, {John A.} and Burley, {Glenn A.}",
year = "2019",
month = "6",
day = "19",
doi = "10.1021/jacs.8b12444",
language = "English",
volume = "141",
pages = "9555--9563",
journal = "Journal of the American Chemical Society",
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publisher = "American Chemical Society",
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TY - JOUR

T1 - Sequence-selective minor groove recognition of a DNA duplex containing synthetic genetic components

AU - Padroni, Giacomo

AU - Withers, Jamie M.

AU - Taladriz Sender, Andrea

AU - Reichenbach, Linus F.

AU - Parkinson, John A.

AU - Burley, Glenn A.

PY - 2019/6/19

Y1 - 2019/6/19

N2 - The structural basis of minor groove recognition of a DNA duplex containing synthetic genetic information by hairpin pyrrole-imidazole polyamides is described. Hairpin polyamides induce a higher melting stabilization of a DNA duplex containing the unnatural P·Z base-pair when an imidazole unit is aligned with a P nucleotide. An NMR structural study showed that the incorporation of two isolated P·Z pairs enlarges the minor groove and slightly narrows the major groove at the site of this synthetic genetic information, relative to a DNA duplex consisting entirely of Watson-Crick base-pairs. Pyrrole-imidazole polyamides bind to a P·Z-containing DNA duplex to form a stable complex, effectively mimicking a G·C pair. A structural hallmark of minor groove recognition of a P·Z pair by a polyamide is the reduced level of allosteric distortion induced by binding of a polyamide to a DNA duplex. Understanding the molecular determinants that influence minor groove recognition of DNA containing synthetic genetic components provides the basis to further develop unnatural base-pairs for synthetic biology applications.

AB - The structural basis of minor groove recognition of a DNA duplex containing synthetic genetic information by hairpin pyrrole-imidazole polyamides is described. Hairpin polyamides induce a higher melting stabilization of a DNA duplex containing the unnatural P·Z base-pair when an imidazole unit is aligned with a P nucleotide. An NMR structural study showed that the incorporation of two isolated P·Z pairs enlarges the minor groove and slightly narrows the major groove at the site of this synthetic genetic information, relative to a DNA duplex consisting entirely of Watson-Crick base-pairs. Pyrrole-imidazole polyamides bind to a P·Z-containing DNA duplex to form a stable complex, effectively mimicking a G·C pair. A structural hallmark of minor groove recognition of a P·Z pair by a polyamide is the reduced level of allosteric distortion induced by binding of a polyamide to a DNA duplex. Understanding the molecular determinants that influence minor groove recognition of DNA containing synthetic genetic components provides the basis to further develop unnatural base-pairs for synthetic biology applications.

KW - DNA

KW - minor groove recognition

KW - unnatural base-pairs

KW - synthetic biology

KW - NMR

UR - https://pubs.acs.org/journal/jacsat

U2 - 10.1021/jacs.8b12444

DO - 10.1021/jacs.8b12444

M3 - Article

VL - 141

SP - 9555

EP - 9563

JO - Journal of the American Chemical Society

T2 - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 24

ER -