Peptide bis-intercalator binds DNA via threading mode with sequence specific contacts in the major groove

Guelev, Vladimir; Lee, Jeeyeon; Ward, Jonathan S.; Sorey, Steven; Hoffman, David W.; Iverson, Brent L.

doi:10.1016/s1074-5521(01)00013-8

Cited by 43 publications

(52 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While it is possible that there are multiple sites on the duplexes for which V1 could bind to form 2:1 complexes, binding of V1 at a second site is not anticipated to be as strong because the ligand bound at the high affinity site, GGTACC, would cover six base pairs and thus presumably hinder the bis-intercalative binding of a second ligand. These results are consistent with solution-based studies of V1 [23] and suggest ESI-MS is a promising tool for the analysis of DNA complexes containing bisintercalators.…”

Section: Complexes With V1supporting

confidence: 87%

“…V1 was found to have a binding preference for d (GGTACC) 2 sequences with NMR results confirming that the -Gly 3 -Lys-peptide scaffold was located in the major groove [23]. The V1-d(GGTACC) 2 complex was formed with a dominant 1:1 binding stoichiometry.…”

Section: Complexes With V1mentioning

confidence: 73%

“…Evaluation of Binding Stoichiometry by ESI-MS-The DNA binding of ligand V1 has been previously examined by NMR and DNAse I footprinting techniques that identified the specific binding sites of this compound [23]. V1 was found to have a binding preference for d (GGTACC) 2 sequences with NMR results confirming that the -Gly 3 -Lys-peptide scaffold was located in the major groove [23].…”

Section: Complexes With V1mentioning

confidence: 99%

“…The primary objective of this study is to evaluate the binding behavior of trans-D1 and cis-C1 which are new ligands containing a rigid spiro-tricyclic scaffold in the trans-and cisorientations, respectively. While few results have been reported for the newer ligands trans-D1 and cis-C1 [25], the binding behavior of V1, the ligand containing the peptide scaffold, has been examined in extensive footprinting and NMR-based studies [22,23]. In the present study, the binding behavior of the well-characterized compound V1 will be examined to establish that the binding behavior observed by ESI-MS can be correlated to the results of traditional solution-based experiments.…”

Section: Introductionmentioning

confidence: 96%

“…A novel class of DNA polyintercalators that shows great promise for binding to long stretches of DNA with sequence specificity and high affinity contain 1,4,5,8-tetracarboxylic naphthalene diimide (NDI) units connected in a head-to-tail arrangement by flexible scaffolds [21][22][23][24] (see Scheme 1). These compounds are known as threading polyintercalators because, upon intercalation, one of the functional groups attached to the diimide nitrogen resides in the DNA major groove, while the other is in the minor groove [21].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Screening of threading bis-intercalators binding to duplex DNA by electrospray ionization tandem mass spectrometry

Mazzitelli

Chu

Reczek

et al. 2007

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

The DNA binding of novel threading bis-intercalators V1, trans-D1, and cis-C1, which contain two naphthalene diimide (NDI) intercalation units connected by a scaffold, was evaluated using electrospray ionization mass spectrometry (ESI-MS) and DNAse footprinting techniques. ESI-MS experiments confirmed that V1, the ligand containing the -Gly 3 -Lys-peptide scaffold, binds to a DNA duplex containing the 5'-GGTACC-3' specific binding site identified in previous NMR-based studies. The ligand formed complexes with a ligand/DNA binding stoichiometry of 1:1, even when there was excess ligand in solution. Trans-D1 and cis-C1 are new ligands containing a rigid spirotricyclic scaffold in the trans-and cis-orientations, respectively. Preliminary DNAse footprinting experiments identified possible specific binding sites of 5'-CAGTGA-5' for trans-D1 and 5'-GGTACC-3' for cis-C1. ESI-MS experiments revealed that both ligands bound to DNA duplexes containing the respective specific binding sequences, with cis-C1 exhibiting the most extensive binding based on a higher fraction of bound DNA value. Cis-C1 formed complexes with a dominant 1:1 binding stoichiometry, whereas trans-D1 was able to form 2:1 complexes at ligand/DNA molar ratios ≥ 1 which is suggestive of non-specific binding. Collisional activated dissociation (CAD) experiments indicate that DNA complexes containing V1, trans-D1, and cis-C1 have a unique fragmentation pathway, which was also observed for complexes containing the commercially available bisintercalator echinomycin, as a result of similar binding interactions, marked by intercalation in addition to hydrogen bonding by the scaffold with the DNA major or minor groove.

show abstract

Section: Complexes With V1supporting

confidence: 87%

Section: Complexes With V1mentioning

confidence: 73%

Section: Complexes With V1mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Screening of threading bis-intercalators binding to duplex DNA by electrospray ionization tandem mass spectrometry

Mazzitelli

Chu

Reczek

et al. 2007

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

show abstract

Foldamers Based on Solvophobic Effects

Zhao¹,

Moore²

2007

Foldamers

View full text Add to dashboard Cite

An Encodable Scaffold for Sequence‐Specific Recognition of Duplex RNA

Kwok,

Yuan,

Arora

2023

Angewandte Chemie

View full text Add to dashboard Cite

RNA, unlike DNA, folds into a multitude of secondary and tertiary structures. This structural diversity has impeded the development of ligands that can sequence‐ specifically target this biomolecule. We sought to develop ligands for double‐stranded RNA (dsRNA) segments, which are ubiquitous in RNA tertiary structure. The major groove of double‐stranded DNA is sequence‐specifically recognized by a range of dimeric helical transcription factors, including the basic leucine zippers (bZIP) and basic helix loop helix (bHLH) proteins; however, such simple structural motifs are not prevalent in RNA‐binding proteins. We interrogated the high‐resolution structures of DNA and RNA to identify requirements for a helix fork motif to occupy dsRNA major grooves akin to dsDNA. Our analysis suggested that the rigidity and angle of approach of dimeric helices in bZIP/bHLH motifs is not ideal for binding of dsRNA major grooves. This investigation revealed that the replacement of the leucine zipper motifs in bHLH proteins with synthetic crosslinkers would allow recognition of dsRNA. We show that a model bHLH DNA‐binding motif does not bind dsRNA but can be reengineered as an RNA ligand. Based on this hypothesis, we rationally designed miniature synthetic crosslinked helix fork (CHF) as a generalizable proteomimetic scaffold for targeting dsRNA.

show abstract

Peptide bis-intercalator binds DNA via threading mode with sequence specific contacts in the major groove

Cited by 43 publications

References 34 publications

Screening of threading bis-intercalators binding to duplex DNA by electrospray ionization tandem mass spectrometry

Screening of threading bis-intercalators binding to duplex DNA by electrospray ionization tandem mass spectrometry

Foldamers Based on Solvophobic Effects

An Encodable Scaffold for Sequence‐Specific Recognition of Duplex RNA

Contact Info

Product

Resources

About