Binding of new cationic porphyrin–tetrapeptide conjugates to nucleoprotein complexes

Orosz, Ádám; Mező, Gábor; Herényi, Levente; Habdas, Jan; Májer, Zsuzsa; Myśliwa-Kurdziel, Beata; Tóth, Katalin; Csı́k, Gabriella

doi:10.1016/j.bpc.2013.03.003

Cited by 8 publications

(8 citation statements)

References 54 publications

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“…These changes reflect the decrease of free porphyrin and increase of bound porphyrin concentration with increasing base pair/porphyrin ratios. However, the alterations of absorption spectra are significantly different from the changes experienced in the case of TMPCP or TMPCP-4P under similar conditions (Mező et al 2011;Orosz et al 2013 The lack of intercalation is also supported by the optical melting results. The strand separation temperature of DNA is slightly increased by the presence of TMPCP-AK.…”

Section: Discussionsupporting

confidence: 68%

“…DNA binding of porphyrin derivatives, and their peptide conjugates was investigated earlier with comprehensive spectroscopic methods. It was found that both porphyrin derivatives and their peptide conjugates can bind to DNA and reflect on at least two distinct binding modes, i.e., intercalation and external binding (Mező et al 2011;Orosz et al 2013). Among others, these binding forms were identified by their absorption bands, since typical absorption spectra of bound forms show characteristic features relative to the free porphyrin: about 20 nm red shift and about 40% hypochromicity of the Soret band for intercalation, and a fewer red shift and about 5% hypochromicity for external binding (Zupan et al 2004;Pasternack et al 1993;Lee et al 2001).…”

Section: Discussionmentioning

confidence: 99%

“…In these conjugates a tetrapeptide (Ac-Lys(H-Ala-D-Ala-Ala)-NH 2 ) (Mező et al 2011;Orosz et al 2013) was attached to meso-tri(4-N-methylpyridyl)-mono-(4-carboxyphenyl)porphyrin (TMPCP) or meso-5,10-bis(4-N-methylpyridyl)-15,20-di-(4-carboxyphenyl)porphyrin (BMPCP).…”

Section: Introductionmentioning

confidence: 99%

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Oligo- and polypeptide conjugates of cationic porphyrins: binding, cellular uptake, and cellular localization

et al. 2017

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Recently we have characterized the DNA and nucleoprotein (NP) binding of bis(4-Nmethylpyridyl)-15,20-di(4-carboxyphenyl)porphyrin (BMPCP) and meso-tri(4-Nmethylpyridyl)-mono(4-carboxyphenyl)porphyrin (TMPCP) and their tetra-peptide conjugates (BMPCP-4P 2 and TMPCP-4P, respectively). In this work we investigated the interaction of TMPCP conjugated to the tetra-peptide branches of branched chain polymeric polypeptide with poly-L-lysine backbone (AK) with DNA or NP using spectroscopic methods.Analysis of absorption spectra revealed the external binding, but no intercalation of TMPCP-AK to DNA. There was no evidence for the interaction between TMPCP-AK and encapsidated DNA. Furthermore, we examined the cellular uptake of BMPCP and TMPCP and their tetra-or polypeptide conjugates by flow cytometry and analyzed how charge, size and structure of the compounds affect their incorporation. In comparison, liposomal association constants of these derivatives were determined. BMPCP-4P 2 accumulated the most, and porphyrins with two positive charges (BMPCP and BMPCP-4P 2 ) showed better accumulation than the tri-cationic TMPCP or TMPCP-4P.Cellular uptake of polycationic TMPCP-AK was significantly lower than that of the free or tetra-peptide conjugated derivatives. The sub-cellular localization of all the five compounds was investigated in co-localization studies by confocal microscopy with special attention to their nuclear localization. Neither free nor conjugated BMPCP or TMPCP were co-localized with nuclear marker. Instead, these derivatives showed co-localization with lysosomal and mitochondrial fluorescent probes. TMPCP-AK conjugate had different localization pattern appearing mainly in mitochondria and cytoplasmic vesicles.Our results may contribute to the further design of DNA targeting porphyrin based constructs.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

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Oligo- and polypeptide conjugates of cationic porphyrins: binding, cellular uptake, and cellular localization

et al. 2017

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“…Using electron microscopy, a massive destruction of virus envelopes was detected after treatment with phthalocyanines containing metal ligands, leading to a significant decrease of virus infectivity of several enveloped viruses [Varicella zoster virus (VZV), HSV-1 and HSV-2], whereas non-enveloped adenovirus was largely resistant to the treatment (Smetana et al 1994). Nevertheless, several studies have presented evidence that non-enveloped viruses are also sensitive to direct PACT inactivation (Kasturi and Platz 1992;Gaspard et al 1995;Costa et al 2008Costa et al , 2010Zupan et al 2008), which might be explained by photoactivated protein crosslinking that leads to direct damage or loss of proteins, and finally the loss of infectivity (Lenard et al 1993;Smetana et al 1997;Orosz et al 2013). At physiological conditions, non-enveloped viruses have negatively charged capsids and enveloped viruses harbour negatively charged glycoproteins on their surface, and are thus likely directly targeted by cationic porphyrins via electrostatic interactions, like previously described for Gram(−) bacteria (Karlin and Brendel 1988;Michen and Graule 2010;Liu et al 2015).…”

Section: Molecular Targets Of Antiviral Pactmentioning

confidence: 99%

Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents

2017

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Photodynamic therapy (PDT) combines a photosensitiser, light and molecular oxygen to induce oxidative stress that can be used to kill pathogens, cancer cells and other highly proliferative cells. There is a growing number of clinically approved photosensitisers and applications of PDT, whose main advantages include the possibility of selective targeting, localised action and stimulation of the immune responses. Further improvements and broader use of PDT could be accomplished by designing new photosensitisers with increased selectivity and bioavailability. Porphyrin-based photosensitisers with amphiphilic properties, bearing one or more positive charges, are an effective tool in PDT against cancers, microbial infections and, most recently, autoimmune skin disorders. The aim of the review is to present some of the recent examples of the applications and research that employ this specific group of photosensitisers. Furthermore, we will highlight the link between their structural characteristics and PDT efficiency, which will be helpful as guidelines for rational design and evaluation of new PSs.

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“…An alternative approach to improve the cellular uptake and the binding of cationic porphyrins to DNA was the introduction at the periphery of the macrocycle of one or two copies of a branched tetrapeptide . A dual mode of interaction of the conjugates to DNA was detected by spectroscopic techniques (intercalation and external binding) and intercalative binding was more feasible with the tricationic conjugate, especially on nucleoprotein complexes . In vitro the uptake of porphyrin–tetrapepeptide conjugate was higher for the dicationic species and their cellular localization was proved in cytoplasmic organelles but not in the nuclear region …”

Section: Biomarkers Detection and Emerging Therapiesmentioning

confidence: 99%

Porphyrin–peptide conjugates in biomedical applications

Biscaglia

Gobbo

2018

Peptide Science

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The conjugation of peptides to porphyrins and related tetrapyrrole based macrocycles have extended their applications in biological systems, where the photophysical properties of these molecules and their ability to coordinate metals can be exploited for detecting and opposing to the onset of important diseases. This review presents a survey of the published literature over last years on biomedical applications of these hybrid compounds, mostly in the field of photodynamic therapy (PDT), but also in sensing key metabolites and peculiar structures of biomolecules in living systems. Peptides based strategies to improve the efficacy of the photosensitizer (PS) in PDT will be discussed, as well as solutions to overcome some limitations recently emerged in the use of peptides as delivery vehicles. An overview on possible application of porphyrin–peptide conjugates in detection of biomarkers of physiological and pathological states will be also presented.

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Binding of new cationic porphyrin–tetrapeptide conjugates to nucleoprotein complexes

Cited by 8 publications

References 54 publications

Oligo- and polypeptide conjugates of cationic porphyrins: binding, cellular uptake, and cellular localization

Oligo- and polypeptide conjugates of cationic porphyrins: binding, cellular uptake, and cellular localization

Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents

Porphyrin–peptide conjugates in biomedical applications

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