Semiquinone Footprinting

Yang, Chia‐Hung; Chen, Wenfu; Jong, Ming-Chu; Jong, Boh-Jun; Chang, Jung-Cheng; Waring, Michael J.; Ma, Lin; Sheh, Leung

doi:10.1021/ja040051m

Cited by 10 publications

(4 citation statements)

References 10 publications

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“…Peptides incorporating such motifs possess excellent DNA binding capability in the sub-micromolar concentration range. [11][12][13][14][15][16] Further attachment of one or more 4-amino-1-methylpyrrole-2-carboxylic acid resi-dues (Py) to XP(Hyp)RK peptides enhances their sequencespecificity toward sequences containing consecutive arrays of A or T nucleotides. 11,[14][15][16] Here we report that peptides HyM-10 and HQ-10 bind satisfactorily to DNA in a sequence-selective manner as assessed by DNase I footprinting.…”

Section: Introductionmentioning

confidence: 99%

Enthalpy-driven nuclease-like activity and mechanism of peptide–chlorambucil conjugates

et al. 2014

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We report the results of attaching the anticancer drug chlorambucil (CLB) to two high-affinity DNA binding peptides: Met-Hyp-Arg-Lys-(Py)4-Lys-Arg-NH2 (HyM-10) and Gln-Hyp-Arg-Lys-(Py)4-Lys-Arg-NH2 (HyQ-10). These CLB-peptide conjugates cleave DNA very effectively and sequence-selectively without the use of chemicals, heat, or UV irradiation. Polyacrylamide gel electrophoresis identifies the sites where CLB-HyM-10 and CLB-HyQ-10 attack a complementary pair of 5'-(32)P-labeled duplexes derived from pBR322 in the absence of piperidine or other chemical additives. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) has confirmed the preferential cleavage sites as well as a novel stepwise cleavage mechanism of sequence-selective DNA cleavage. Resembling restriction endonucleases, the CLB-peptide conjugates appear to be capable of producing double strand DNA breaks. Circular dichroism studies show that CLB-HyM-10 and CLB-HyQ-10 induce significant local conformational changes in DNA via the minor groove, possibly with dimeric binding stoichiometry. The energetic basis of DNA binding by these conjugates has been investigated by isothermal titration calorimetry, revealing that the binding of both the peptides and their CLB conjugates is overwhelmingly enthalpy-driven. The maintenance of a conserved negative binding free energy in DNA-conjugate interactions is a crucial feature of the universal enthalpy-entropy compensation phenomenon. The strongly enthalpy-driven binding of CLB-peptide conjugates to preferred loci in DNA furnishes the required proximity effect to generate the observed nuclease-like sequence-selective cleavage.

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Section: Introductionmentioning

confidence: 99%

Enthalpy-driven nuclease-like activity and mechanism of peptide–chlorambucil conjugates

et al. 2014

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“…[1][2][3][4] Extensive studies have been carried out with small ligands that are capable of sequence-specific recognition of DNA including drugs, 1-3 antitumor antibiotics, [4][5][6][7] netropsin/distamycin and its analogues, [8][9][10][11][12][13] and synthetic peptides. [14][15][16][17] Previously we introduced a novel XPRK peptide motif as a basis for sequence-selective interaction studies. [14][15][16][17] The design of this motif stems from a naturally occurring SPXX motif 18,19 found in repeating sequences in histones, steroid hormone receptors, various segmentation gene products and some oncogene products.…”

Section: Introductionmentioning

confidence: 99%

“…[14][15][16][17] Previously we introduced a novel XPRK peptide motif as a basis for sequence-selective interaction studies. [14][15][16][17] The design of this motif stems from a naturally occurring SPXX motif 18,19 found in repeating sequences in histones, steroid hormone receptors, various segmentation gene products and some oncogene products. It was suggested that the SPXX motif assumes a b-turn stabilized by two hydrogen bonds, and that the side chains of the two basic residues engage in salt bridges with the DNA phosphate groups.…”

Section: Introductionmentioning

confidence: 99%

“…This prompted us to focus on molecular aspects of cooperative interactions between peptides and DNA. In our early sequence-specificity studies with synthetic molecules containing both the XPRK motif [14][15][16][17] as well as the polyamide motif we found a number of peptides that exhibit notable sequence-selectivity in binding to particular sites on the DNA duplex. Among these peptides we identified a nonapeptide His-Hyp-Arg-Lys-(Py) 3 -Lys-Arg-NH 2 (PyHyp-9) and a dodecapeptide His-Hyp-Arg-Lys-(Py) 4 -His-HypArg-Lys-NH 2 (PyHyp-12) that displayed significant cooperativity in binding to DNA.…”

Section: Introductionmentioning

confidence: 99%

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Detection of multiple network-based allosteric interactions between peptides and arrays of DNA binding sites

Kao

Huang

Yang

et al. 2010

Bioorganic & Medicinal Chemistry

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Unusually Strong Positive Cooperativity in Binding of Peptides to Latent Membrane Protein‐1 DNA Fragments of the Epstein–Barr Viral Gene

et al. 2006

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The DNA-binding preferences of two oligopeptide amides, (His-Pro-Arg-Lys)(3)NH(2) (HR-12) and (Ser-Pro-Arg-Lys)(3)NH(2) (SP-12), have been examined by quantitative DNase I footprinting studies. Two different DNA fragments were investigated: a pair of 5'-(32)P-labeled duplexes from pBR322 with one or other of the complementary strands labeled and a corresponding pair of 5'-(32)P-labeled duplexes representing fragments of the latent membrane protein (LMP-1) gene from a pathogenic Epstein-Barr virus variant derived from nasopharyngeal carcinoma. The major objective was to examine molecular recognition and cooperative features associated with sequence-selective binding of synthetic peptides to the LMP-1 fragments. At various binding sites on the pBR322 fragments, Hill coefficients (n(H)) ranging from 1.9-2.2 were observed; these results indicate modest positive cooperativity between binding sites for both peptides. By contrast, unusually high values of n(H), ranging from 4.0-9.3, were observed at various binding sites on the LMP-1 fragments. Allosteric models can be constructed to interpret the observed cooperative interactions between different DNA recognition sites in the LMP-1 gene upon binding of the peptide ligands. It is noteworthy that these models feature a novel network of cooperativity interconnecting multiple DNA allosteric sites. The evidence of sequence selectivity and strong cooperativity discovered in this work may prove to be a general feature of peptide interactions with some nucleic acids.

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Semiquinone Footprinting

Cited by 10 publications

References 10 publications

Enthalpy-driven nuclease-like activity and mechanism of peptide–chlorambucil conjugates

Enthalpy-driven nuclease-like activity and mechanism of peptide–chlorambucil conjugates

Detection of multiple network-based allosteric interactions between peptides and arrays of DNA binding sites

Unusually Strong Positive Cooperativity in Binding of Peptides to Latent Membrane Protein‐1 DNA Fragments of the Epstein–Barr Viral Gene

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