DNA sequence-specific recognition of peptides incorporating the HPRK and polyamide motifs

Chang, Jung-Cheng; Yang, Chia‐Hung; Chou, Ping-Yen; Yang, Wenting; Chou, I-Chun; Lu, Ching-Tai; Lin, Pei‐Hsuan; Hou, Rolis Chien-Wei; Jeng, Kee-Ching; Cheng, Chien‐Chuan; Sheh, Leung

doi:10.1016/j.bmc.2003.10.049

Cited by 7 publications

(3 citation statements)

References 29 publications

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“…Full protocols for footprinting experiments have been published previously. 11,14,15 4.4. DNA cleavage induced by CLB-peptide conjugates Radiolabeled pBR322 DNA fragments: 158-mer DNA duplex (upper strand 5′-32 P-labeled) and 135-mer DNA duplex (lower strand 5′-32 P-labeled) were prepared by PCR amplification in a thermal cycler (ABI model 9700) as previously described.…”

Section: Dnase I Footprintingmentioning

confidence: 99%

“…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%

“…[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. Polyacrylamide gel electrophoresis is ideal for exploring the sequence-selectivity of DNA cleavage by the CLB-peptide conjugates CLB-HyM-10 and CLB-HyQ-10.…”

Section: Introductionmentioning

confidence: 99%

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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: Dnase I Footprintingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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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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Determination of Allosteric Effects and Interstrand Bidentate Interactions in DNA‐Peptide Molecular Recognition

Chen

Huang

Jeng

et al. 2010

J Chinese Chemical Soc

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To study DNA allostery, quantitative DNase I footprinting studies were carried out on a newly designed peptide His-Hyp-Lys-Lys-(Py) 4 -Lys-Lys-NH 2 (HypKK-10) containing the XHypKK (Hyp = hydroxyproline) and polyamide motifs. The interconnection of DNA footprints of peptides HypKK-10 and the parent peptide PyPro-12 supports the proposal that interaction network cooperativity is preferred in DNA-peptide interactions between multiple recognition sites. A simple method of determining interstrand bidentate interactions between the peptide moieties and DNA bases is introduced. It is envisaged that interstrand bidentate interactions also participate in the relay of conformational changes to recognition sites on the complementary strands. Circular dichroism studies of the titration of peptide HypKK-10 with an oligonucleotide duplex indicate that this peptide binds in a dimeric fashion to DNA in the minor groove. This work may prompt the design of new DNA binding ligands for the study of DNA-peptide allosteric interactions and DNA interaction network.

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DNA sequence-specific recognition of peptides incorporating the HPRK and polyamide motifs

Cited by 7 publications

References 29 publications

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

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

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

Determination of Allosteric Effects and Interstrand Bidentate Interactions in DNA‐Peptide Molecular Recognition

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