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State-of-the-Art Macromolecules in Italy
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State-of-the-Art Macromolecules in Italy

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Macromolecules".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 11639

Special Issue Editors

Dr. Menotti Ruvo

E-Mail Website
Guest Editor
Istituto di Biostrutture e Bioimmagini, CNR, 80134 Napoli, Italy
Interests: monoclonal antibodies; antibody functional fragments; antibody drug conjugates; peptide libraries
Special Issues, Collections and Topics in MDPI journals
Dr. Dario Puppi

E-Mail Website
Guest Editor
Department of Chemistry and Industrial Chemistry, University of Pisa, 56126 Pisa, Italy
Interests: biomaterials; tissue engineering; biodegradable polymers; polyhydroxyalkanoates; polymeric composites; additive manufacturing; electrospinning
Special Issues, Collections and Topics in MDPI journals
Dr. Annamaria Sandomenico

E-Mail Website
Guest Editor
Istituto di Biostrutture e Bioimmagini, CNR, 80134 Napoli, Italy
Interests: proteins; protein expression; molecular biology; cell culture
Special Issues, Collections and Topics in MDPI journals
Dr. Nunzianna Doti

E-Mail Website
Guest Editor
Institute of Biostructures and Bioimaging (IBB)-CNR, Via Mezzocannone 16, 80134 Naples, Italy
Interests: peptides; peptidomimetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to announce a call for submissions for a Special Issue of the International Journal of Molecular Sciences dedicated to the development of novel biotherapeutics in Italy, including bioactive peptides, recombinant proteins, natural and plasma-derived proteins, monoclonal antibodies, antibody fragments, DNA and RNA fragments, PNAs, other DNA/RNA surrogates, and bio-materials. A deeper understanding of the molecular, structural, functional and analytical properties of these molecules is the main requirement to progress towards their preclinical and possibly clinical testing in both academic and industrial research groups, and papers on these topics are often the seminal works in their development as valuable products. We therefore encourage the submission of research articles, reviews and commentaries on one or more of these topics by Italian research groups of all backgrounds who are actively working in this field.  

Dr. Menotti Ruvo
Dr. Dario Puppi
Dr. Annamaria Sandomenico
Dr. Nunzianna Doti
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bioactive peptides
  • protein biotherapeutics
  • protein–protein interactions
  • antibodies
  • antibody fragments
  • protein aggregation
  • peptide libraries
  • DNA- and RNA-based bioactive molecules
  • DNA and RNA surrogates
  • bio-materials

Published Papers (5 papers)

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Research

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15 pages, 1982 KiB  
Article
Ctp1 and Yhm2: Two Mitochondrial Citrate Transporters to Support Metabolic Flexibility of Saccharomyces cerevisiae
by Graziana Assalve, Paola Lunetti, Vincenzo Zara and Alessandra Ferramosca
Int. J. Mol. Sci. 2024, 25(3), 1870; https://doi.org/10.3390/ijms25031870 - 3 Feb 2024
Cited by 1 | Viewed by 862
Abstract
Differently from higher eukaryotic cells, in the yeast Saccharomyces cerevisiae there are two mitochondrial carrier proteins involved in the transport of citrate: Ctp1 and Yhm2. Very little is known about the physiological role of these proteins. Wild-type and mutant yeast strains deleted in [...] Read more.
Differently from higher eukaryotic cells, in the yeast Saccharomyces cerevisiae there are two mitochondrial carrier proteins involved in the transport of citrate: Ctp1 and Yhm2. Very little is known about the physiological role of these proteins. Wild-type and mutant yeast strains deleted in CTP1 and YHM2 were grown in media supplemented with a fermentable (glucose) or a nonfermentable (ethanol) carbon source. To assess changes in Ctp1 and Yhm2 mRNA expression levels, real-time PCR was performed after total RNA extraction. In the wild-type strain, the metabolic switch from the exponential to the stationary phase is associated with an increase in the expression level of the two citrate transporters. In addition, the results obtained in the mutant strains suggest that the presence of a single citrate transporter can partially compensate for the absence of the other. Ctp1 and Yhm2 differently contribute to fermentative and respiratory metabolism. Moreover, the two mitochondrial carriers represent a link between the Krebs cycle and the glyoxylate cycle, which play a key role in the metabolic adaptation strategies of S. cerevisiae. Full article
(This article belongs to the Special Issue State-of-the-Art Macromolecules in Italy)
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16 pages, 2262 KiB  
Article
Synthesis, Conformational Analysis and Antitumor Activity of the Naturally Occurring Antimicrobial Medium-Length Peptaibol Pentadecaibin and Spin-Labeled Analogs Thereof
by Laura Morbiato, Celeste Quaggia, Luca Menilli, Chiara Dalla Torre, Antonio Barbon and Marta De Zotti
Int. J. Mol. Sci. 2023, 24(17), 13396; https://doi.org/10.3390/ijms241713396 - 29 Aug 2023
Viewed by 849
Abstract
Peptaibols are proteolysis-resistant, membrane-active peptides. Their remarkably stable helical 3D-structures are key for their bioactivity. They can insert themselves into the lipid bilayer as barrel staves, or lay on its surface like carpets, depending on both their length and the thickness of the [...] Read more.
Peptaibols are proteolysis-resistant, membrane-active peptides. Their remarkably stable helical 3D-structures are key for their bioactivity. They can insert themselves into the lipid bilayer as barrel staves, or lay on its surface like carpets, depending on both their length and the thickness of the lipid bilayer. Medium-length peptaibols are of particular interest for studying the peptide–membrane interaction because their length allows them to adopt either orientation as a function of the membrane thickness, which, in turn, might even result in an enhanced selectivity. Electron paramagnetic resonance (EPR) is the election technique used to this aim, but it requires the synthesis of spin-labeled medium-length peptaibols, which, in turn, is hampered by the poor reactivity of the Cα-tetrasubstituted residues featured in their sequences. After several years of trial and error, we are now able to give state-of-the-art advice for a successful synthesis of nitroxide-containing peptaibols, avoiding deleted sequences, side reactions and difficult purification steps. Herein, we describe our strategy and itsapplication to the synthesis of spin-labeled analogs of the recently discovered, natural, medium-length peptaibol pentadecaibin. We studied the antitumor activity of pentadecaibin and its analogs, finding potent cytotoxicity against human triple-negative breast cancer and ovarian cancer. Finally, our analysis of the peptide conformational preferences and membrane interaction proved that pentadecaibinspin-labeling does not alter the biological features of the native sequence and is suitable for further EPR studies. The nitroxide-containing pentadecaibins, and their synthetic strategy described herein, will help to shed light on the mechanism of the peptide–membrane interaction of medium-length peptaibols. Full article
(This article belongs to the Special Issue State-of-the-Art Macromolecules in Italy)
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14 pages, 2170 KiB  
Article
Oxidized Substrates of APEH as a Tool to Study the Endoprotease Activity of the Enzyme
by Annamaria Sandomenico, Marta Gogliettino, Emanuela Iaccarino, Carmela Fusco, Andrea Caporale, Menotti Ruvo, Gianna Palmieri and Ennio Cocca
Int. J. Mol. Sci. 2022, 23(1), 443; https://doi.org/10.3390/ijms23010443 - 31 Dec 2021
Cited by 1 | Viewed by 1603
Abstract
APEH is a ubiquitous and cytosolic serine protease belonging to the prolyl oligopeptidase (POP) family, playing a critical role in the processes of degradation of proteins through both exo- and endopeptidase events. Endopeptidase activity has been associated with protein oxidation; however, the actual [...] Read more.
APEH is a ubiquitous and cytosolic serine protease belonging to the prolyl oligopeptidase (POP) family, playing a critical role in the processes of degradation of proteins through both exo- and endopeptidase events. Endopeptidase activity has been associated with protein oxidation; however, the actual mechanisms have yet to be elucidated. We show that a synthetic fragment of GDF11 spanning the region 48–64 acquires sensitivity to the endopeptidase activity of APEH only when the methionines are transformed into the corresponding sulphoxide derivatives. The data suggest that the presence of sulphoxide-modified methionines is an important prerequisite for the substrates to be processed by APEH and that the residue is crucial for switching the enzyme activity from exo- to endoprotease. The cleavage occurs on residues placed on the C-terminal side of Met(O), with an efficiency depending on the methionine adjacent residues, which thereby may play a crucial role in driving and modulating APEH endoprotease activity. Full article
(This article belongs to the Special Issue State-of-the-Art Macromolecules in Italy)
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Review

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18 pages, 4233 KiB  
Review
Assembly of the Multi-Subunit Cytochrome bc1 Complex in the Yeast Saccharomyces cerevisiae
by Vincenzo Zara, Gabriella De Blasi and Alessandra Ferramosca
Int. J. Mol. Sci. 2022, 23(18), 10537; https://doi.org/10.3390/ijms231810537 - 11 Sep 2022
Cited by 5 | Viewed by 3479
Abstract
The cytochrome bc1 complex is an essential component of the mitochondrial respiratory chain of the yeast Saccharomyces cerevisiae. It is composed of ten protein subunits, three of them playing an important role in electron transfer and proton pumping across the inner mitochondrial [...] Read more.
The cytochrome bc1 complex is an essential component of the mitochondrial respiratory chain of the yeast Saccharomyces cerevisiae. It is composed of ten protein subunits, three of them playing an important role in electron transfer and proton pumping across the inner mitochondrial membrane. Cytochrome b, the central component of this respiratory complex, is encoded by the mitochondrial genome, whereas all the other subunits are of nuclear origin. The assembly of all these subunits into the mature and functional cytochrome bc1 complex is therefore a complicated process which requires the participation of several chaperone proteins. It has been found that the assembly process of the mitochondrial bc1 complex proceeds through the formation of distinct sub-complexes in an ordered sequence. Most of these sub-complexes have been thoroughly characterized, and their molecular compositions have also been defined. This study critically analyses the results obtained so far and highlights new possible areas of investigation. Full article
(This article belongs to the Special Issue State-of-the-Art Macromolecules in Italy)
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42 pages, 9507 KiB  
Review
Polymeric Hydrogels for In Vitro 3D Ovarian Cancer Modeling
by Simona Braccini, Chiara Tacchini, Federica Chiellini and Dario Puppi
Int. J. Mol. Sci. 2022, 23(6), 3265; https://doi.org/10.3390/ijms23063265 - 17 Mar 2022
Cited by 10 | Viewed by 4102
Abstract
Ovarian cancer (OC) grows and interacts constantly with a complex microenvironment, in which immune cells, fibroblasts, blood vessels, signal molecules and the extracellular matrix (ECM) coexist. This heterogeneous environment provides structural and biochemical support to the surrounding cells and undergoes constant and dynamic [...] Read more.
Ovarian cancer (OC) grows and interacts constantly with a complex microenvironment, in which immune cells, fibroblasts, blood vessels, signal molecules and the extracellular matrix (ECM) coexist. This heterogeneous environment provides structural and biochemical support to the surrounding cells and undergoes constant and dynamic remodeling that actively promotes tumor initiation, progression, and metastasis. Despite the fact that traditional 2D cell culture systems have led to relevant medical advances in cancer research, 3D cell culture models could open new possibilities for the development of an in vitro tumor microenvironment more closely reproducing that observed in vivo. The implementation of materials science and technology into cancer research has enabled significant progress in the study of cancer progression and drug screening, through the development of polymeric scaffold-based 3D models closely recapitulating the physiopathological features of native tumor tissue. This article provides an overview of state-of-the-art in vitro tumor models with a particular focus on 3D OC cell culture in pre-clinical studies. The most representative OC models described in the literature are presented with a focus on hydrogel-based scaffolds, which guarantee soft tissue-like physical properties as well as a suitable 3D microenvironment for cell growth. Hydrogel-forming polymers of either natural or synthetic origin investigated in this context are described by highlighting their source of extraction, physical-chemical properties, and application for 3D ovarian cancer cell culture. Full article
(This article belongs to the Special Issue State-of-the-Art Macromolecules in Italy)
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