RESUMO
Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase holoenzyme, which adds telomeric DNA repeats on chromosome ends to counteract telomere shortening. In addition, there is evidence of TERT non-canonical functions, among which is an antioxidant role. In order to better investigate this role, we tested the response to X-rays and H2O2 treatment in hTERT-overexpressing human fibroblasts (HF-TERT). We observed in HF-TERT a reduced induction of reactive oxygen species and an increased expression of the proteins involved in the antioxidant defense. Therefore, we also tested a possible role of TERT inside mitochondria. We confirmed TERT mitochondrial localization, which increases after oxidative stress (OS) induced by H2O2 treatment. We next evaluated some mitochondrial markers. The basal mitochondria quantity appeared reduced in HF-TERT compared to normal fibroblasts and an additional reduction was observed after OS; nevertheless, the mitochondrial membrane potential and morphology were better conserved in HF-TERT. Our results suggest a protective function of TERT against OS, also preserving mitochondrial functionality.
Assuntos
Antioxidantes , Telomerase , Humanos , Antioxidantes/metabolismo , Peróxido de Hidrogênio/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo , Telomerase/metabolismoRESUMO
Mutations in many genes that control the expression, the function, or the stability of telomerase cause telomere biology disorders (TBDs), such as dyskeratosis congenita, pulmonary fibrosis, and aplastic anemia. Mutations in a subset of the genes associated with TBDs cause reductions of the telomerase RNA moiety hTR, thus limiting telomerase activity. We have recently found that loss of the trimethylguanosine synthase TGS1 increases both hTR abundance and telomerase activity and leads to telomere elongation. Here, we show that treatment with the S-adenosylmethionine analog sinefungin inhibits TGS1 activity, increases the hTR levels, and promotes telomere lengthening in different cell types. Our results hold promise for restoring telomere length in stem and progenitor cells from TBD patients with reduced hTR levels.
Assuntos
MetiltransferasesRESUMO
Atomic force microscopy (AFM) is a scanning probe technique that allows visualization of biological samples with a nanometric resolution. Determination of the physical properties of biological molecules at a single-molecule level is achieved through topographic analysis of the sample adsorbed on a flat and smooth surface. AFM has been widely used for the structural analysis of nucleic acid-protein interactions, providing insights on binding specificity and stoichiometry of proteins forming complexes with DNA substrates. Analysis of single-stranded DNA-binding proteins by AFM requires specific single-stranded/double-stranded hybrid DNA molecules as substrates for protein binding. In this chapter we describe the protocol for AFM characterization of binding properties of Drosophila telomeric protein Ver using DNA constructs that mimic the structure of chromosome ends. We provide details on the methodology used, including the procedures for the generation of DNA substrates, the preparation of samples for AFM visualization, and the data analysis of AFM images. The presented procedure can be adapted for the structural studies of any single-stranded DNA-binding protein.
Assuntos
DNA de Cadeia Simples/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Proteínas de Ligação a Telômeros/metabolismo , Animais , DNA de Cadeia Simples/química , Drosophila melanogaster/genética , Microscopia de Força Atômica , Ligação Proteica , Imagem Individual de Molécula , Telômero/genética , Telômero/metabolismoRESUMO
Biogenesis of the human telomerase RNA (hTR) involves a complex series of posttranscriptional modifications, including hypermethylation of the 5' mono-methylguanosine cap to a tri-methylguanosine cap (TMG). How the TMG cap affects hTR maturation is unknown. Here, we show that depletion of trimethylguanosine synthase 1 (TGS1), the enzyme responsible for cap hypermethylation, increases levels of hTR and telomerase. Diminished trimethylation increases hTR association with the cap-binding complex (CBC) and with Sm chaperone proteins. Loss of TGS1 causes an increase in accumulation of mature hTR in both the nucleus and the cytoplasm compared with controls. In TGS1 mutant cells, increased hTR assembles with telomerase reverse transcriptase (TERT) protein to yield elevated active telomerase complexes and increased telomerase activity, resulting in telomere elongation in cultured human cells. Our results show that TGS1-mediated hypermethylation of the hTR cap inhibits hTR accumulation, restrains levels of assembled telomerase, and limits telomere elongation.
Assuntos
Metiltransferases/deficiência , RNA/metabolismo , Telomerase/metabolismo , Telômero/metabolismo , Biocatálise , Corpos Enovelados/metabolismo , Guanosina/metabolismo , Células HEK293 , Células HeLa , Humanos , Metilação , Metiltransferases/genética , Modelos Biológicos , Mutação/genética , Poliadenilação , Capuzes de RNA/metabolismo , Frações Subcelulares/metabolismoRESUMO
In this paper, the selective interactions of synthetic derivatives of two natural compounds, berberine and palmatine, with DNA G-quadruplex structures were reported. In particular, the previous works on this subject concerning berberine were further presented and discussed, whereas the results concerning palmatine are presented here for the first time. In detail, these palmatine derivatives were developed by inserting seven different small peptide basic chains, giving several new compounds that have never been reported before. The preliminary studies of the interactions of these compounds with various G-quadruplex-forming sequences were carried out by means of various structural and biochemical techniques, which showed that the presence of suitable side chains is very useful for improving the interaction of the ligands with G-quadruplex structures. Thus, these new palmatine derivatives might act as potential anticancer drugs.
Assuntos
Alcaloides de Berberina/síntese química , Berberina/análogos & derivados , DNA/metabolismo , Berberina/química , Alcaloides de Berberina/química , Alcaloides de Berberina/farmacologia , DNA/química , Quadruplex G , Ligantes , Modelos Moleculares , Estrutura MolecularRESUMO
SMN (Survival Motor Neuron) deficiency is the predominant cause of spinal muscular atrophy (SMA), a severe neurodegenerative disorder that can lead to progressive paralysis and death. Although SMN is required in every cell for proper RNA metabolism, the reason why its loss is especially critical in the motor system is still unclear. SMA genetic models have been employed to identify several modifiers that can ameliorate the deficits induced by SMN depletion. Here we focus on WDR79/TCAB1, a protein important for the biogenesis of several RNA species that has been shown to physically interact with SMN in human cells. We show that WDR79 depletion results in locomotion defects in both Drosophila and Caenorhabditis elegans similar to those elicited by SMN depletion. Consistent with this observation, we find that SMN overexpression rescues the WDR79 loss-of-function phenotype in flies. Most importantly, we also found that WDR79 overexpression ameliorates the locomotion defects induced by SMN depletion in both flies and worms. Our results collectively suggest that WDR79 and SMN play evolutionarily conserved cooperative functions in the nervous system and suggest that WDR79/TCAB1 may have the potential to modify SMA pathogenesis.
Assuntos
Proteínas de Drosophila/metabolismo , Locomoção/fisiologia , Transtornos dos Movimentos/etiologia , Atrofia Muscular Espinal/complicações , Proteínas de Ligação a RNA/metabolismo , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans , Modelos Animais de Doenças , Drosophila , Proteínas de Drosophila/genética , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Neurônios Motores/patologia , Atrofia Muscular Espinal/genética , Fenótipo , Interferência de RNA/fisiologia , Proteínas de Ligação a RNA/genética , Proteína 1 de Sobrevivência do Neurônio MotorRESUMO
Drosophila telomeres are sequence-independent structures maintained by transposition to chromosome ends of three specialized retroelements rather than by telomerase activity. Fly telomeres are protected by the terminin complex that includes the HOAP, HipHop, Moi and Ver proteins. These are fast evolving, non-conserved proteins that localize and function exclusively at telomeres, protecting them from fusion events. We have previously suggested that terminin is the functional analogue of shelterin, the multi-protein complex that protects human telomeres. Here, we use electrophoretic mobility shift assay (EMSA) and atomic force microscopy (AFM) to show that Ver preferentially binds single-stranded DNA (ssDNA) with no sequence specificity. We also show that Moi and Ver form a complex in vivo. Although these two proteins are mutually dependent for their localization at telomeres, Moi neither binds ssDNA nor facilitates Ver binding to ssDNA. Consistent with these results, we found that Ver-depleted telomeres form RPA and γH2AX foci, like the human telomeres lacking the ssDNA-binding POT1 protein. Collectively, our findings suggest that Drosophila telomeres possess a ssDNA overhang like the other eukaryotes, and that the terminin complex is architecturally and functionally similar to shelterin.
Assuntos
Dano ao DNA , DNA de Cadeia Simples/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Ligação a Telômeros/metabolismo , Telômero/metabolismo , Animais , Proteínas Cromossômicas não Histona/fisiologia , Reparo do DNA , DNA de Cadeia Simples/ultraestrutura , Drosophila/genética , Proteínas de Drosophila/química , Proteínas de Drosophila/fisiologia , Proteínas de Drosophila/ultraestrutura , Microscopia de Força Atômica , Domínios Proteicos , Multimerização Proteica , Proteína de Replicação A/metabolismo , Proteínas de Ligação a Telômeros/química , Proteínas de Ligação a Telômeros/ultraestruturaRESUMO
Regulatory regions in the genome can act through a variety of mechanisms that range from the occurrence of histone modifications to the presence of protein-binding loci for self-annealing sequences. The final result is often the induction of a conformational change of the DNA double helix, which alters the accessibility of a region to transcription factors and consequently gene expression. A â¼300 kb regulatory region on chromosome 14 at the 3' end (3'RR) of immunoglobulin (Ig) heavy-chain genes shows very peculiar features, conserved in mammals, including enhancers and transcription factor binding sites. In primates, the 3'RR is present in two copies, both having a central enhancer named hs1.2. We previously demonstrated the association between different hs1.2 alleles and Ig plasma levels in immunopathology. Here, we present the analysis of a putative G-quadruplex structure (tetraplex) consensus site embedded in a variable number tandem repeat (one to four copies) of hs1.2 that is a distinctive element among the enhancer alleles, and an investigation of its three-dimensional structure using bioinformatics and spectroscopic approaches. We suggest that both the role of the enhancer and the alternative effect of the hs1.2 alleles may be achieved through their peculiar three-dimensional-conformational rearrangement. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 768-778, 2016.
Assuntos
Alelos , Elementos Facilitadores Genéticos , Quadruplex G , Imunoglobulina G/genética , Cadeias Pesadas de Imunoglobulinas/genética , Animais , Humanos , Imunoglobulina G/biossíntese , Cadeias Pesadas de Imunoglobulinas/biossínteseRESUMO
A novel approach to cancer therapeutics is emerging in the field of G-quadruplex (G4) ligands, small molecules designed to stabilize four-stranded structures that can form at telomeres as well as in other genomic sequences, including oncogene promoter sequences, 5'-UTR regions and introns. In this study, we investigated the binding activity of perylene and coronene derivatives PPL3C, CORON and EMICORON to G4 structures formed within the promoter regions of two important cancer-related genes, c-MYC and BCL-2, and their biochemical effects on gene and protein expression. In order to fully characterize the ability of the selected ligands to bind and stabilize the G4 structures originated by the c-MYC and BCL-2 promoter sequences, we performed electrospray ionization mass spectrometry (ESI-MS), Fluorescence Resonance Energy Transfer (FRET) measurements, Circular Dichroism (CD) spectra and polymerase stop assay. Altogether our results showed that the ligands had a high capacity in binding and stabilizing the G4 structures within the c-MYC and BCL-2 promoter sequences in vitro. Notably, when we evaluated by quantitative real-time PCR and western blotting analysis, the effects of treatment with the different G4 ligands on c-MYC and BCL2 expression in a human melanoma cell line, EMICORON appeared the most effective compound in reducing the mRNA and protein levels of both genes. These results encourage to consider EMICORON as a promising example of multimodal class of an antineoplastic drug, affecting different tumor crucial pathways simultaneously: telomere maintenance (as previously described), cell proliferation and apoptosis via down-regulation of both c-MYC and BCL-2 (this paper).
Assuntos
Sequência Rica em GC , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Melanoma , Oncogenes , Perileno , Compostos Policíclicos , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-bcl-2 , Proteínas Proto-Oncogênicas c-myc , Linhagem Celular Tumoral , Humanos , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/metabolismo , Perileno/farmacocinética , Perileno/farmacologia , Compostos Policíclicos/farmacocinética , Compostos Policíclicos/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-myc/biossíntese , Proteínas Proto-Oncogênicas c-myc/genéticaRESUMO
Telomeres are nucleoprotein complexes that protect the ends of linear chromosomes from incomplete replication, degradation and detection as DNA breaks. Mammalian telomeres are protected by shelterin, a multiprotein complex that binds the TTAGGG telomeric repeats and recruits a series of additional factors that are essential for telomere function. Although many shelterin-associated proteins have been so far identified, the inventory of shelterin-interacting factors required for telomere maintenance is still largely incomplete. Here, we characterize AKTIP/Ft1 (human AKTIP and mouse Ft1 are orthologous), a novel mammalian shelterin-bound factor identified on the basis of its homology with the Drosophila telomere protein Pendolino. AKTIP/Ft1 shares homology with the E2 variant ubiquitin-conjugating (UEV) enzymes and has been previously implicated in the control of apoptosis and in vesicle trafficking. RNAi-mediated depletion of AKTIP results in formation of telomere dysfunction foci (TIFs). Consistent with these results, AKTIP interacts with telomeric DNA and binds the shelterin components TRF1 and TRF2 both in vivo and in vitro. Analysis of AKTIP- depleted human primary fibroblasts showed that they are defective in PCNA recruiting and arrest in the S phase due to the activation of the intra S checkpoint. Accordingly, AKTIP physically interacts with PCNA and the RPA70 DNA replication factor. Ft1-depleted p53-/- MEFs did not arrest in the S phase but displayed significant increases in multiple telomeric signals (MTS) and sister telomere associations (STAs), two hallmarks of defective telomere replication. In addition, we found an epistatic relation for MST formation between Ft1 and TRF1, which has been previously shown to be required for replication fork progression through telomeric DNA. Ch-IP experiments further suggested that in AKTIP-depleted cells undergoing the S phase, TRF1 is less tightly bound to telomeric DNA than in controls. Thus, our results collectively suggest that AKTIP/Ft1 works in concert with TRF1 to facilitate telomeric DNA replication.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas/metabolismo , Telômero/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Proteínas Reguladoras de Apoptose/química , Proteínas Reguladoras de Apoptose/genética , Ciclo Celular/genética , Células Cultivadas , Dano ao DNA/genética , Replicação do DNA , Proteínas de Drosophila/química , Proteínas de Drosophila/metabolismo , Fibroblastos/fisiologia , Genes p53 , Humanos , Camundongos , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Proteínas/genética , Telômero/genética , Proteína 1 de Ligação a Repetições Teloméricas/metabolismo , Proteína 2 de Ligação a Repetições Teloméricas/metabolismoRESUMO
The ends of eukaryotic chromosomes need to be protected from the activation of a DNA damage response that leads the cell to replicative senescence or apoptosis. In mammals, protection is accomplished by a six-factor complex named shelterin, which organizes the terminal TTAGGG repeats in a still ill-defined structure, the telomere. The stable interaction of shelterin with telomeres mainly depends on the binding of two of its components, TRF1 and TRF2, to double-stranded telomeric repeats. Tethering of TRF proteins to telomeres occurs in a chromatin environment characterized by a very compact nucleosomal organization. In this work we show that binding of TRF1 and TRF2 to telomeric sequences is modulated by the histone octamer. By means of in vitro models, we found that TRF2 binding is strongly hampered by the presence of telomeric nucleosomes, whereas TRF1 binds efficiently to telomeric DNA in a nucleosomal context and is able to remodel telomeric nucleosomal arrays. Our results indicate that the different behavior of TRF proteins partly depends on the interaction with histone tails of their divergent N-terminal domains. We propose that the interplay between the histone octamer and TRF proteins plays a role in the steps leading to telomere deprotection.
Assuntos
Nucleossomos/metabolismo , Telômero/metabolismo , Proteína 1 de Ligação a Repetições Teloméricas/metabolismo , Proteína 2 de Ligação a Repetições Teloméricas/metabolismo , Sítios de Ligação , DNA/metabolismo , Histonas/metabolismo , Nucleossomos/química , Ligação Proteica , Estrutura Terciária de Proteína , Sequências Repetitivas de Ácido Nucleico , Telômero/química , Proteína 1 de Ligação a Repetições Teloméricas/química , Proteína 2 de Ligação a Repetições Teloméricas/químicaRESUMO
Following the results we previously reported on a series of xanthene and xanthone derivatives as G-quadruplex stabilizing ligands, in order to obtain a more selective compound with respect to the previous generation of derivatives, we decided to modify the structure of the core ligand, specifically its aromatic extension. In particular, here we report the design, synthesis and activity data of a new compound obtained by dimerization of the xanthene core (HELIXA4C). The reported results show that extension of the aromatic core and the increase of the number of polar side chains led to a great enhancement of G-quadruplex selectivity and telomere damage capability, as derived using ESI-MS evaluation, in vitro cancer screening and specific immunofluorescence assays.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Quadruplex G/efeitos dos fármacos , Telômero/efeitos dos fármacos , Xantonas/química , Xantonas/farmacologia , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dimerização , Humanos , Simulação de Acoplamento Molecular , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Xantonas/síntese químicaRESUMO
The establishment of a specific nucleoprotein structure, the telomere, is required to ensure the protection of chromosome ends from being recognized as DNA damage sites. Telomere shortening below a critical length triggers a DNA damage response that leads to replicative senescence. In normal human somatic cells, characterized by telomere shortening with each cell division, telomere uncapping is a regulated process associated with cell turnover. Nevertheless, telomere dysfunction has also been associated with genomic instability, cell transformation, and cancer. Despite the essential role telomeres play in chromosome protection and in tumorigenesis, our knowledge of the chromatin structure involved in telomere maintenance is still limited. Here we review the recent findings on chromatin modifications associated with the dynamic changes of telomeres from protected to deprotected state and their role in telomere functions.
RESUMO
Telomerase is responsible for the immortal phenotype of cancer cells and telomerase inhibition may specifically target cancer cell proliferation. Ligands able to selectively bind to G-quadruplex telomeric DNA have been considered as telomerase inhibitors but their mechanisms of action have often been deduced from a non-quantitative telomerase activity assay (TRAP assay) that involves a PCR step and that does not provide insight on the mechanism of inhibition. Furthermore, quadruplex ligands have also been shown to exert their effects by affecting association of telomere binding proteins with telomeres. Here, we use quantitative direct telomerase activity assays to evaluate the strength and mechanism of action of hydrosoluble perylene diimides (HPDIs). HPDIs contain a perylene moiety and different numbers of positively charged side chains. Side chain features vary with regard to number and distances of the charges. IC(50) values of HPDIs were in the low micromolar (0.5-5 µM) range depending on the number and features of the side chains. HPDIs having four side chains emerged as the best compounds of this series. Analysis of primer elongation products demonstrated that at low HPDI concentrations, telomerase inhibition involved formation of telomeric G-quadruplex structures, which inhibited further elongation by telomerase. At high HPDI concentrations, telomerase inhibition occurred independently of G-quadruplex formation of the substrate. The mechanism of action of HPDIs and their specific binding to G-quadruplex DNA was supported by PAGE analysis, CD spectroscopy and ESI-MS. Finally, competition Telospot experiments with duplex DNA indicated specific binding of HPDIs to the single-stranded telomeric substrates over double stranded DNA, a result supported by competitive ESI-MS. Altogether, our results indicate that HPDIs act by stabilizing G-quadruplex structures in single-stranded telomeric DNA, which in turn prevents repeat addition processivity of telomerase.
Assuntos
Quadruplex G/efeitos dos fármacos , Imidas/farmacologia , Perileno/análogos & derivados , Telomerase/metabolismo , Telômero/metabolismo , Dicroísmo Circular , Humanos , Perileno/farmacologia , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
hTERT core promoter regulates telomerase transcription in human cells, thus its structural features are of large interest. We have found that the G-rich hTERT core promoter region, corresponding to the major DNase I hypersensitive site in chromatin organization, contains nine putative G-quadruplex forming sequences (PQS) and is unfavorable for nucleosome formation. Here we show that four PQS are effectively able to form stable parallel intramolecular G-quadruplexes, using PAGE and CD spectroscopy analysis. The PQS-region, as a whole, appears to be organized in three self-interacting G-quadruplexes, probably giving rise to a helicoidal superstructure, as shown by CD and polymerase stop assay. POL-HPDI drugs, that we previously found useful in selectively stabilizing telomeric G-quadruplex, are able to stabilize both the single intramolecular G-quadruplex and the PQS-region superstructure. The features of their induced CD spectra suggest that POL-HPDIs bind to single G-quadruplexes and to whole PQS-region superstructure, mainly by end-stacking interactions.
Assuntos
Quadruplex G , Perileno/química , Poliaminas/química , Telomerase/genética , Sequência de Bases , Dicroísmo Circular , Eletroforese em Gel de Poliacrilamida , Humanos , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Oligonucleotídeos/química , Regiões Promotoras GenéticasRESUMO
The human telomeric G-quadruplex structure is a promising target for the design of cancer drugs. The selectivity of G-quadruplex ligands with respect to duplex genomic DNA is of especial importance. The high selectivity of polyamine conjugated perylene derivatives appears to be regulated by side-chain charge density, as indicated by data from a FRET melting assay and induced CD spectroscopy.
Assuntos
Antineoplásicos/química , Quadruplex G , Perileno/química , Dicroísmo Circular , Transferência Ressonante de Energia de Fluorescência , Humanos , Ligantes , Poliaminas/química , Telomerase/antagonistas & inibidores , Telomerase/metabolismo , Telômero/químicaRESUMO
The search for telomerase inhibitors has been widely explored in the last few years, since telomerase activity in somatic cells can be considered as a general cancer mark. One of the possible strategies is the capping of telomere 3'-end (the enzyme substrate) in a conformation not available to the recognition of telomerase, with particular attention to G-quadruplex structures. Small organic molecules, able to induce and/or stabilize G-quadruplexes, have been synthesized and studied in many different research groups. Here, we mean to critically analyze the class of hydrosoluble perylene di-imides (HPDIs), which offers the intriguing possibility to fix the hydrophobic molecule moiety (perylene) able to bind to the terminal G-quartet of telomeric G-quadruplex, while widely varying the number and features of the hydrophilic side chains, which interact with the DNA grooves. We will show that, using the strategy, it is possible to significantly improve HPDIs efficiency in inhibiting telomerase and their selectivity for telomeric G-quadruplex with respect to duplex genomic DNA.
Assuntos
Inibidores Enzimáticos/química , Quadruplex G , Perileno/análogos & derivados , Telomerase/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Humanos , Perileno/química , Perileno/farmacologia , Telomerase/metabolismo , Água/químicaRESUMO
We have synthesized eight polyamine perylene diimides to conjugate the efficiency of perylene derivatives in stabilizing G-quadruplex structures and the polyamines' biological activity, due to specific interactions with different DNA domains. Our study was carried out by investigating the ability of these derivatives to induce inter- and intramolecular G-quadruplex structures by polyacrylamide gel electrophoresis (PAGE) and to inhibit telomerase in a modified TRAP assay. The two properties appear to be satisfactorily correlated and they show that the number and distances of positive charges in the side chains dramatically influence both these features. Although our previous studies on perylene derivatives with mono-positively charged side chains indicated that self assembly in aqueous solution leads to a major efficiency, the result observed with the spermine derivative suggests that a too strong aggregation is unfavourable, because it determines a lower solubility of the compounds.