Profiles

Carmine Pasquale Cerrato

Doktorand

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Arbetar vid Institutionen för neurokemi
Telefon 08-16 42 64
E-post carmine@neurochem.su.se
Besöksadress Svante Arrheniusväg 16 B
Rum M 412
Postadress Institutionen för neurokemi 106 91 Stockholm

Publikationer

I urval från Stockholms universitets publikationsdatabas
  • 2014. Carmine Pasquale Cerrato, Tõnis Lehto, Ülo Langel.

    Peptides and peptide-cargo complexes have been used for drug delivery and gene therapy. One of the most used delivery vectors are cell-penetrating peptides, due to their ability to be taken up by a variety of cell types and deliver a large variety of cargoes through the cell membrane with low cytotoxicity. In vitro and in vivo studies have shown their possibility and full effectiveness to deliver oligonucleotides, plasmid DNA, small interfering RNAs, antibodies, and drugs. We report in this review some of the latest strategies for peptide-mediated delivery of nucleic acids. It focuses on peptide-based vectors for therapeutic molecules and on nucleic acid delivery. In addition, we discuss recent applications and clinical trials.

  • 2015. Carmine Pasquale Cerrato (et al.). The FASEB Journal 29 (11), 4589-4599

    Cell-penetrating peptides (CPPs) are short, nontoxic peptides with cationic and/or amphipathic properties able to cross the cellular membrane. CPPs are used for the delivery of a wide variety of cargoes, such as proteins, oligonucleotides, and therapeutic molecules. The aim of the present study was to synthesize unusually small novel CPPs targeting mitochondria based on the Szeto-Schiller peptide (SS-31) to influence intramitochondrial processes and to improve the biologic effects. All the peptides used were synthesized manually using 9-fluorenylmethyloxycarbonyl chemistry. In the first part of the study, HeLa 705, U87, and bEnd.3 cells were used as in vitro delivery model. Cells were incubated for 24 h at 37°C and 5% CO2 with different concentrations of our peptides. Cell proliferation assay was performed to evaluate cell viability. Biologic effects such as mitochondrial membrane potential and antioxidant activity were evaluated. H2O2 was used as positive control. Uptake studies were performed using peptides conjugated with 5(6)-carboxyfluorescein (FAM). Fluorescent microscopy was used to determine presence and localization of peptides into the cells. Isolated mitochondria from pretreated cells and mitochondria treated after isolation were used to confirm the targeting ability of the peptide. Uptake of FAM alone was used as negative control. Microscopy studies confirmed the ability of peptides to penetrate cell. Localization analysis showed increase in uptake by 35% compared with SS-31. Mitochondrial CPP 1 (mtCPP-1) had no effect on mitochondrial membrane potential and prevented reactive oxygen species formation in bEnd.3 cells by 2-fold compared with SS-31. No cytotoxicity was observed even at high concentration (100 µM). These data suggest that mtCPP-1 is a mitochondrial CPP and protect mitochondria from oxidative damage due to its own antioxidant activities.-Cerrato, C. P., Pirisinu M., Vlachos E. N., Langel, Ü. Novel cell-penetrating peptide targeting mitochondria.

  • 2015. Carmine Pasquale Cerrato, Ülo Langel, Lena Mäler.

    More than twenty years after the discovery of the first cell-penetrating peptide (CPP), a large number of both naturally occurring as well as engineered CPPs have been discovered. Generally, CPPs are short polycationic sequences of less than 30 amino acids that are able to translocate different cargoes into cells. They are amphipathic and net positively charged at physiological pH. The cargo can be covalently attached to the CPP, which can be achieved by expression as a fusion construct or by chemical coupling; or the cargo and carrier could bind each other non-covalently mainly through ionic interactions.

    A series of CPPs targeting mitochondria (mtCPPs) were studied in an effort to optimize their applications for the reduction of reactive oxygen species targeting this therapeutically important organelle. Mitochondria have evolved to play a vital role in both life and death of eukaryotic cells, through involvement in numerous cellular functions, such as the proficient production of energy from ATP biosynthesis and the regulation of programmed cell death. As a result, dysfunction in the biochemical processes housed within this organelle is implicated in diverse diseases, including cancer, diabetes, and neurodegenerative disorders. Advancing mitochondrial medicine by probing the subcellular biochemistry or targeting therapeutics into this organelle has motivated the development of effective mitochondrial delivery vectors. A fluorescent probe was covalently attached at the N-terminus of the analog peptides to determine the cellular internalization and the possibility to be transported to mitochondria by mtCPPs. The results report the development of a novel cationic peptides (mtCPP-1), which is readily cell permeable and preferentially localize into the mitochondria of living mammalian cells. By substitutions with both natural and synthetic amino acids, and monitoring the intracellular localization by fluorescence microscopy, the mitochondrial accumulation with a cationic peptide was achieved. The biological and chemical characterization of mtCPP-1 revealed the importance of balancing the opposing characteristics of positive charge and lipophilicity to attain preferential sequestration into mitochondria, as well as provide evidence that this antioxidant peptide will be suitable as mitochondrial delivery vector.

  • 2015. Carmine Cerrato, Kadi-Liis Veiman, Ülo Langel. Advances in the Discovery and Development of Peptide Therapeutics, 160-171
Visa alla publikationer av Carmine Pasquale Cerrato vid Stockholms universitet

Senast uppdaterad: 16 augusti 2017

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