Interactions of diastereomeric tripeptides of lysyl-5-fluorotryptophyllysine with DNA. 1. Optical and fluorine-19 NMR studies of native DNA complexes

Shine, Nancy R.; James, Thomas Leroy

doi:10.1021/bi00337a012

Cited by 11 publications

(6 citation statements)

References 38 publications

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“…1 and 2). These results are in agreement with earlier reports 15,20,24 of similar oligopeptides assuming an extended ␤-sheet upon binding to DNA where an aromatic residue next to an N-terminal lysine is in an ideal position to establish strong stacking interactions with DNA base pairs. The upfield chemical shifts for 1 in the presence of poly(dA-dT) 2 were even higher than with CT-DNA, and upfield shifts of Ϫ0.35 ppm for H 3 ,H 5 and Ϫ0.31 ppm for H 2 ,H 6 were obtained at a peptide to nucleic acid base ratio of 1.…”

Section: Resultssupporting

confidence: 93%

Partial intercalation with nucleic acids of peptides containing aromatic and basic amino acids

et al. 1999

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Section: Resultssupporting

confidence: 93%

Partial intercalation with nucleic acids of peptides containing aromatic and basic amino acids

et al. 1999

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“…Drug molecules containing fluorine have been used to probe interactions with macromolecules using 19 F NMR [22,29]. Other fluorine-containing agonist and antagonist adenosine receptor ligands have been reported [1,2].…”

Section: Discussionmentioning

confidence: 99%

Molecular probes for extracellular adenosine receptors

Jacobson

Ukena

Padgett

et al. 1987

Biochemical Pharmacology

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Derivatives of adenosine receptor agonists (N 6 -phenyladenosines) and antagonists (1,3-dialkyl-8-phenylxanthines) bearing functionalized chains suitable for attachment to other molecules have been reported [Jacobson et al., J. med. Chem. 28, 1334 and 1341]. The "functionalized congener" approach has been extended to the synthesis of spectroscopic and other probes for adenosine receptors that retain high affinity (K i ~ 10 −9 −10 −8 M) in A 1 -receptor binding. The probes have been synthesized from an antagonist xanthine amine congener (XAC) and an adenosine amine congener (ADAC). [ 3 H]ADAC has been synthesized and found to bind highly specifically to A 1 -adenosine receptors of rat and calf cerebral cortical membranes with K D values of 1.4 and 0.34 nM respectively. The higher affinity in the bovine brain, seen also with many of the probes derived from ADAC and XAC, is associated with phenyl substituents. The spectroscopic probes contain a reporter group attached at a distal site of the functionalized chain. These bifunctional ligands may contain a spin label (e.g. the nitroxyl radical TEMPO) for electron spin resonance spectroscopy, or a fluorescent dye, including fluorescein and 4-nitrobenz-2-oxa-1,3-diazole (NBD), or labels for 19 F nuclear magnetic resonance spectroscopy. Potential applications of the spectroscopic probes in characterization of adenosine receptors are discussed."Functionalized congener" refers to a drug derivative that contains a chemical functional group, such as an amine or carboxylic acid, attached through a spacer chain to a position on the pharmacophore, which position is relatively insensitive to steric bulk. The congeners are designed as intermediates for the synthesis of covalent conjugates that retain binding properties at the receptor site for the drug. The aims of this approach are 2-fold: (1) to develop potential new pharmaceutical agents in which the activity of the primary pharmacophore (portion of drug molecule essential for biological activity) may be modulated through distal changes, and (2) to synthesize radioactive and non-radioactive molecular probes for the drug binding site. Since the strategy of this drug design allows groups to be placed at a distance from the binding site of the primary pharmacophore, it is possible to overcome constraints on the size of the attached group [1][2][3][4][5].Sites for functionalization of adenosine receptor ligands have been identified for both agonists (derivatives of N 6 -phenyladenosine) and antagonists (derivatives of 1,3-dialkyl-8-phenylxanthine . A common structure-activity relationship (SAR) feature in both agonist and antagonist series is that the presence of a distal amino group located on the attached chain in many cases results in increased affinity to adenosine receptors.In this study we have examined the parameters of binding of tritiated ADAC and have demonstrated the utility of both ADAC and XAC as synthetic precursors for receptor probes. Biotin-containing probes for adenosine receptors have been reported [6]. ...

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“…For this reason, stacking interactions have been studied in short oligonucleotide fragments10, 11 and other model compounds 12. The existence of stacking between aromatic side chains and DNA nucleobases is indicated by evidence from a number of different techniques, such as changes in the fluorescence spectra of the aromatic residues, alterations in the circular dichroism spectra, etc 13–18. Some models of stacking or intercalative binding between peptides containing aromatic residues and short DNA fragments have been proposed based on NMR data 19–21.…”

Section: Introductionmentioning

confidence: 99%

Solution Structure and Stability of Tryptophan‐Containing Nucleopeptide Duplexes

et al. 2003

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Covalently linked peptide-oligonucleotide hybrids were used as models for studying tryptophan-DNA interactions. The structure and stability of several hybrids in which peptides and oligonucleotides are linked through a phosphodiester bond between the hydroxy group of a homoserine (Hse) side chain and the 3'-end of the oligonucleotide, have been studied by both NMR and CD spectroscopy and by restrained molecular dynamics methods. The three-dimensional solution structure of the complex between Ac-Lys-Trp-Lys-Hse(p3'dGCATCG)-Ala-OH (p=phosphate, Ac=acetyl) and its complementary strand 5'dCGTAGC has been determined from a set of 276 experimental NOE distances and 33 dihedral angle constraints. The oligonucleotide structure is a well-defined duplex that belongs to the B-form family of DNA structures. The covalently linked peptide adopts a folded structure in which the tryptophan side chain stacks against the 3'-terminal guanine moiety, which forms a cap at the end of the duplex. This stacking interaction, which resembles other tryptophan-nucleobase interactions observed in some protein-DNA complexes, is not observed in the single-stranded form of Ac-Lys-Trp-Lys-Hse(p3'dGCATCG)-Ala-OH, where the peptide chain is completely disordered. A comparison with the pure DNA duplex, d(5'GCTACG3')-(5'CGTAGC3'), indicates that the interaction between the peptide and the DNA contributes to the stability of the nucleopeptide duplex. The different contributions that stabilize this complex have been evaluated by studying other nucleopeptide compounds with related sequences.

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Interactions of diastereomeric tripeptides of lysyl-5-fluorotryptophyllysine with DNA. 1. Optical and fluorine-19 NMR studies of native DNA complexes

Cited by 11 publications

References 38 publications

Partial intercalation with nucleic acids of peptides containing aromatic and basic amino acids

Partial intercalation with nucleic acids of peptides containing aromatic and basic amino acids

Molecular probes for extracellular adenosine receptors

Solution Structure and Stability of Tryptophan‐Containing Nucleopeptide Duplexes

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