A class of Trp-Trp-AA-OBzl: Synthesis, in vitro anti-proliferation/in vivo anti-tumor evaluation, intercalation-mechanism investigation and 3D QSAR analysis

Zhang, Xiaoyi; Yang, Yifan; Zhao, Ming; Liu, Liu; Zheng, Meiqing; Wang, Yuji; Wu, Jianhui; Peng, Shiqi

doi:10.1016/j.ejmech.2011.05.004

Cited by 15 publications

(5 citation statements)

References 24 publications

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“…In our previous papers, the diverse intercalators of DNA were reported 21–25. On the other hand, however, their effective dose reached 8.9 μmol/kg/day.…”

Section: Introductionmentioning

confidence: 96%

<p>BCESA: a nano-scaled intercalator capable of targeting tumor tissue and releasing anti-tumoral β-carboline-3-carboxylic acid</p>

Cui

Zhang

et al. 2019

IJN

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Background: In the discovery of DNA intercalators, β-carbolines compose one member of the most interesting alkaloid family and are of clinical importance. In the efforts, N-(3-benzyloxycarbonyl-β-carboline-1-yl)ethyl-Ser-Ala-OBzl (BCESA) was designed as a nano-scaled DNA intercalator without Dox-like toxicity. Methods: Based on the structural analysis and CDOCKER energy comparison, BCESA was rationally designed as such a nano-scaled intercalator. The anti-tumor activity, the toxicity and the tumor targeting action of BCESA were evaluated on mouse models. Results: The in vitro proliferation of cancer cells, but not non-cancer cells, was effectively inhibited by BCESA. On S180 mouse model BCESA dose-dependently slowed the tumor growth, and 0.01 μmol/kg/day was found as a minimal effective dose. Both BCESA and its moiety were found in the tumor tissue, but not in the organs and the blood, of S180 mice. Conclusion: BCESA should be a nano-scaled intercalator capable of targeting tumor tissue to release anti-tumoral β-carboline-3-carboxylic acid and its 1-methyl derivative, while Ser-Ala-OBzl is a simple and desirable carrier.

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“…In our previous papers, the diverse intercalators of DNA were reported 21–25. On the other hand, however, their effective dose reached 8.9 μmol/kg/day.…”

Section: Introductionmentioning

confidence: 96%

<p>BCESA: a nano-scaled intercalator capable of targeting tumor tissue and releasing anti-tumoral β-carboline-3-carboxylic acid</p>

Cui

Zhang

et al. 2019

IJN

Self Cite

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“…Since canonic amino acids are involved in polynucleotide recognition, their incorporation in oligopeptides can be used in DNA sensing, as was demonstrated for tripeptides containing bis-tryptophan units [20]. Furthermore, peptide-binding units can easily be functionalized by fluorophores [21,22], providing tools for DNA fluorescent labeling and visualization [23].…”

Section: Introductionmentioning

confidence: 99%

Dipeptides Containing Pyrene and Modified Photochemically Reactive Tyrosine: Noncovalent and Covalent Binding to Polynucleotides

Sviben,

Glavaš,

Erben

et al. 2023

Molecules

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Dipeptides 1 and 2 were synthesized from unnatural amino acids containing pyrene as a fluorescent label and polynucleotide binding unit, and modified tyrosine as a photochemically reactive unit. Photophysical properties of the peptides were investigated by steady-state and time-resolved fluorescence. Both peptides are fluorescent (Φf = 0.3–0.4) and do not show a tendency to form pyrene excimers in the concentration range < 10−5 M, which is important for their application in the fluorescent labeling of polynucleotides. Furthermore, both peptides are photochemically reactive and undergo deamination delivering quinone methides (QMs) (ΦR = 0.01–0.02), as indicated from the preparative photomethanolysis study of the corresponding N-Boc protected derivatives 7 and 8. Both peptides form stable complexes with polynucleotides (log Ka > 6) by noncovalent interactions and similar affinities, binding to minor grooves, preferably to the AT reach regions. Peptide 2 with a longer spacer between the fluorophore and the photo-activable unit undergoes a more efficient deamination reaction, based on the comparison with the N-Boc protected derivatives. Upon light excitation of the complex 2·oligoAT10, the photo-generation of QM initiates the alkylation, which results in the fluorescent labeling of the oligonucleotide. This study demonstrated, as a proof of principle, that small molecules can combine dual forms of fluorescent labeling of polynucleotides, whereby initial addition of the dye rapidly forms a reversible high-affinity noncovalent complex with ds-DNA/RNA, which can be, upon irradiation by light, converted to the irreversible (covalent) form. Such a dual labeling ability of a dye could have many applications in biomedicinal sciences.

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“…However, canonic amino acids can also be involved in the polynucleotide recognition, as it is the case in nature. For example, binding to DNA was demonstrated for tripeptides containing bis-tryptophan units [ 21 , 22 ]. Owing to tryptophan fluorescence, the binding can also be monitored by fluorescence spectroscopy.…”

Section: Introductionmentioning

confidence: 99%

Non-Covalent Binding of Tripeptides-Containing Tryptophan to Polynucleotides and Photochemical Deamination of Modified Tyrosine to Quinone Methide Leading to Covalent Attachment

et al. 2021

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A series of tripeptides TrpTrpPhe (1), TrpTrpTyr (2), and TrpTrpTyr[CH2N(CH3)2] (3) were synthesized, and their photophysical properties and non-covalent binding to polynucleotides were investigated. Fluorescent Trp residues (quantum yield in aqueous solvent ΦF = 0.03–0.06), allowed for the fluorometric study of non-covalent binding to DNA and RNA. Moreover, high and similar affinities of 2×HCl and 3×HCl to all studied double stranded (ds)-polynucleotides were found (logKa = 6.0–6.8). However, the fluorescence spectral responses were strongly dependent on base pair composition: the GC-containing polynucleotides efficiently quenched Trp emission, at variance to AT- or AU-polynucleotides, which induced bisignate response. Namely, addition of AT(U) polynucleotides at excess over studied peptide induced the quenching (attributed to aggregation in the grooves of polynucleotides), whereas at excess of DNA/RNA over peptide the fluorescence increase of Trp was observed. The thermal denaturation and circular dichroism (CD) experiments supported peptides binding within the grooves of polynucleotides. The photogenerated quinone methide (QM) reacts with nucleophiles giving adducts, as demonstrated by the photomethanolysis (quantum yield ΦR = 0.11–0.13). Furthermore, we have demonstrated photoalkylation of AT oligonucleotides by QM, at variance to previous reports describing the highest reactivity of QMs with the GC reach regions of polynucleotides. Our investigations show a proof of principle that QM precursor can be imbedded into a peptide and used as a photochemical switch to enable alkylation of polynucleotides, enabling further applications in chemistry and biology.

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A class of Trp-Trp-AA-OBzl: Synthesis, in vitro anti-proliferation/in vivo anti-tumor evaluation, intercalation-mechanism investigation and 3D QSAR analysis

Cited by 15 publications

References 24 publications

<p>BCESA: a nano-scaled intercalator capable of targeting tumor tissue and releasing anti-tumoral β-carboline-3-carboxylic acid</p>

<p>BCESA: a nano-scaled intercalator capable of targeting tumor tissue and releasing anti-tumoral β-carboline-3-carboxylic acid</p>

Dipeptides Containing Pyrene and Modified Photochemically Reactive Tyrosine: Noncovalent and Covalent Binding to Polynucleotides

Non-Covalent Binding of Tripeptides-Containing Tryptophan to Polynucleotides and Photochemical Deamination of Modified Tyrosine to Quinone Methide Leading to Covalent Attachment

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A class of Trp-Trp-AA-OBzl: Synthesis, in vitro anti-proliferation/in vivo anti-tumor evaluation, intercalation-mechanism investigation and 3D QSAR analysis

Cited by 15 publications

References 24 publications

<p>BCESA: a nano-scaled intercalator capable of targeting tumor tissue and releasing anti-tumoral &beta;-carboline-3-carboxylic acid</p>

<p>BCESA: a nano-scaled intercalator capable of targeting tumor tissue and releasing anti-tumoral &beta;-carboline-3-carboxylic acid</p>

Dipeptides Containing Pyrene and Modified Photochemically Reactive Tyrosine: Noncovalent and Covalent Binding to Polynucleotides

Non-Covalent Binding of Tripeptides-Containing Tryptophan to Polynucleotides and Photochemical Deamination of Modified Tyrosine to Quinone Methide Leading to Covalent Attachment

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<p>BCESA: a nano-scaled intercalator capable of targeting tumor tissue and releasing anti-tumoral β-carboline-3-carboxylic acid</p>

<p>BCESA: a nano-scaled intercalator capable of targeting tumor tissue and releasing anti-tumoral β-carboline-3-carboxylic acid</p>