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Synthetic Peptides and Peptidomimetics: From Basic Science to Biomedical Applications

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

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 52043

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Special Issue Editors

Dr. Nunzianna Doti

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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

Dr. Menotti Ruvo

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Guest Editor

Istituto di Biostrutture e Bioimmagini, CNR, 80134 Napoli, Italy
Interests: monoclonal antibodies; antibody functional fragments; antibody drug conjugates
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

Synthetic peptides are gaining increasing interest as both research tools in basic and applied science and as therapeutic and diagnostic agents in clinical settings. Their use as inhibitors of protein–protein interactions is becoming a common practice toward elucidating the binding mode of proteins, advancing our understanding of signaling cascades, and offering a viable contribution to the design and development of new drugs. Synthetic peptides are also ideal ligands for extracellular receptors, acting as potent activators of several cellular pathways such as those of the immune response. To date, about 60 peptides have been approved for human use worldwide, many of which are derived from natural molecules, and hundreds more are progressing through the different stages of clinical trials. However, the poor membrane permeability, short plasma half-life, and scarce oral bioavailability strongly limit their druggability and negatively impact on clinical aspects. In this scenario, novel structural modifications are continuously sought for improving pharmacokinetic properties. Among others, amino acid or backbone modifications and the introduction of non-natural amino acids and conjugation of chemical moieties that extend the half-life, improve cellular uptake, stabilize active conformations, and modulate solubility are constantly proposed. Given the high biocompatibility, generally low toxicity, and functionalization potential, peptides and peptidomimetics are also being increasingly employed to develop new functional biomaterials which are excellent cell culture substrates for medicinal applications or that may act as biorecognition elements for the detection of analytes such as proteins, nucleic acids, and pathogens. In this instance, peptides are also being used as recognition units for chip-based biosensors for clinical diagnosis.

We therefore invite academic and industrial investigators working in all these fields to submit original research articles or reviews describing and discussing the most recent advancements and developments in basic science and biomedical applications.

Potential topics include, but are not limited to:

Synthetic peptides and peptidomimetics as protein–protein inhibitors
Synthetic procedures for preparing peptides and peptidomimetics
Biochemical and biophysical characterization of peptides and peptidomimetics
Peptide-based bioconjugation
Nanoparticle-conjugated peptides
Peptide-based bioreceptors
Peptide-based biomaterials

Dr. Nunzianna Doti
Dr. Menotti Ruvo
Guest Editors

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Published Papers (13 papers)

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12 pages, 1354 KiB

Open AccessCommunication

Relevance of AIF/CypA Lethal Pathway in SH-SY5Y Cells Treated with Staurosporine

by Mariarosaria Conte, Rosanna Palumbo, Alessandra Monti, Elisabetta Fontana, Angela Nebbioso, Menotti Ruvo, Lucia Altucci and Nunzianna Doti

Int. J. Mol. Sci. 2022, 23(1), 265; https://doi.org/10.3390/ijms23010265 - 27 Dec 2021

Cited by 5 | Viewed by 3539

Abstract

The AIF/CypA complex exerts a lethal activity in several rodent models of acute brain injury. Upon formation, it translocates into the nucleus of cells receiving apoptotic stimuli, inducing chromatin condensation, DNA fragmentation, and cell death by a caspase-independent mechanism. Inhibition of this complex in a model of glutamate-induced cell death in HT-22 neuronal cells by an AIF peptide (AIF(370-394)) mimicking the binding site on CypA, restores cell survival and prevents brain injury in neonatal mice undergoing hypoxia-ischemia without apparent toxicity. Here, we explore the effects of the peptide on SH-SY5Y neuroblastoma cells stimulated with staurosporine (STS), a cellular model widely used to study Parkinson’s disease (PD). This will pave the way to understanding the role of the complex and the potential therapeutic efficacy of inhibitors in PD. We find that AIF(370-394) confers resistance to STS-induced apoptosis in SH-SY5Y cells similar to that observed with CypA silencing and that the peptide works on the AIF/CypA translocation pathway and not on caspases activation. These findings suggest that the AIF/CypA complex is a promising target for developing novel therapeutic strategies against PD. Full article

(This article belongs to the Special Issue Synthetic Peptides and Peptidomimetics: From Basic Science to Biomedical Applications)

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17 pages, 2156 KiB

Open AccessArticle

Pharmacologically Targeting the Fibroblast Growth Factor 14 Interaction Site on the Voltage-Gated Na⁺ Channel 1.6 Enables Isoform-Selective Modulation

by Nolan M. Dvorak, Cynthia M. Tapia, Aditya K. Singh, Timothy J. Baumgartner, Pingyuan Wang, Haiying Chen, Paul A. Wadsworth, Jia Zhou and Fernanda Laezza

Int. J. Mol. Sci. 2021, 22(24), 13541; https://doi.org/10.3390/ijms222413541 - 17 Dec 2021

Cited by 4 | Viewed by 2852

Abstract

Voltage-gated Na⁺ (Na_v) channels are the primary molecular determinant of the action potential. Among the nine isoforms of the Na_v channel α subunit that have been described (Na_v1.1-Na_v1.9), Na_v1.1, Na_v1.2, and Na_v1.6 are the primary isoforms expressed in the central nervous system (CNS). Crucially, these three CNS Na_v channel isoforms display differential expression across neuronal cell types and diverge with respect to their subcellular distributions. Considering these differences in terms of their localization, the CNS Na_v channel isoforms could represent promising targets for the development of targeted neuromodulators. However, current therapeutics that target Na_v channels lack selectivity, which results in deleterious side effects due to modulation of off-target Na_v channel isoforms. Among the structural components of the Na_v channel α subunit that could be pharmacologically targeted to achieve isoform selectivity, the C-terminal domains (CTD) of Na_v channels represent promising candidates on account of displaying appreciable amino acid sequence divergence that enables functionally unique protein–protein interactions (PPIs) with Na_v channel auxiliary proteins. In medium spiny neurons (MSNs) of the nucleus accumbens (NAc), a critical brain region of the mesocorticolimbic circuit, the PPI between the CTD of the Na_v1.6 channel and its auxiliary protein fibroblast growth factor 14 (FGF14) is central to the generation of electrical outputs, underscoring its potential value as a site for targeted neuromodulation. Focusing on this PPI, we previously developed a peptidomimetic derived from residues of FGF14 that have an interaction site on the CTD of the Na_v1.6 channel. In this work, we show that whereas the compound displays dose-dependent effects on the activity of Na_v1.6 channels in heterologous cells, the compound does not affect Na_v1.1 or Na_v1.2 channels at comparable concentrations. In addition, we show that the compound correspondingly modulates the action potential discharge and the transient Na+ of MSNs of the NAc. Overall, these results demonstrate that pharmacologically targeting the FGF14 interaction site on the CTD of the Na_v1.6 channel is a strategy to achieve isoform-selective modulation, and, more broadly, that sites on the CTDs of Na_v channels interacted with by auxiliary proteins could represent candidates for the development of targeted therapeutics. Full article

(This article belongs to the Special Issue Synthetic Peptides and Peptidomimetics: From Basic Science to Biomedical Applications)

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27 pages, 5288 KiB

Open AccessArticle

Conformational Preferences and Antiproliferative Activity of Peptidomimetics Containing Methyl 1′-Aminoferrocene-1-carboxylate and Turn-Forming Homo- and Heterochiral Pro-Ala Motifs

by Monika Kovačević, Mojca Čakić Semenčić, Kristina Radošević, Krešimir Molčanov, Sunčica Roca, Lucija Šimunović, Ivan Kodrin and Lidija Barišić

Int. J. Mol. Sci. 2021, 22(24), 13532; https://doi.org/10.3390/ijms222413532 - 16 Dec 2021

Cited by 7 | Viewed by 2789

Abstract

The concept of peptidomimetics is based on structural modifications of natural peptides that aim not only to mimic their 3D shape and biological function, but also to reduce their limitations. The peptidomimetic approach is used in medicinal chemistry to develop drug-like compounds that are more active and selective than natural peptides and have fewer side effects. One of the synthetic strategies for obtaining peptidomimetics involves mimicking peptide α-helices, β-sheets or turns. Turns are usually located on the protein surface where they interact with various receptors and are therefore involved in numerous biological events. Among the various synthetic tools for turn mimetic design reported so far, our group uses an approach based on the insertion of different ferrocene templates into the peptide backbone that both induce turn formation and reduce conformational flexibility. Here, we conjugated methyl 1′-aminoferrocene-carboxylate with homo- and heterochiral Pro-Ala dipeptides to investigate the turn formation potential and antiproliferative properties of the resulting peptidomimetics 2–5. Detailed spectroscopic (IR, NMR, CD), X-ray and DFT studies showed that the heterochiral conjugates 2 and 3 were more suitable for the formation of β-turns. Cell viability study, clonogenic assay and cell death analysis showed the highest biological potential of homochiral peptide 4. Full article

(This article belongs to the Special Issue Synthetic Peptides and Peptidomimetics: From Basic Science to Biomedical Applications)

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24 pages, 7805 KiB

Open AccessArticle

Environment-Sensitive Fluorescent Labelling of Peptides by Luciferin Analogues

by Marialuisa Siepi, Rosario Oliva, Antonio Masino, Rosa Gaglione, Angela Arciello, Rosita Russo, Antimo Di Maro, Anna Zanfardino, Mario Varcamonti, Luigi Petraccone, Pompea Del Vecchio, Marcello Merola, Elio Pizzo, Eugenio Notomista and Valeria Cafaro

Int. J. Mol. Sci. 2021, 22(24), 13312; https://doi.org/10.3390/ijms222413312 - 10 Dec 2021

Cited by 1 | Viewed by 3124

Abstract

Environment-sensitive fluorophores are very valuable tools in the study of molecular and cellular processes. When used to label proteins and peptides, they allow for the monitoring of even small variations in the local microenvironment, thus acting as reporters of conformational variations and binding events. Luciferin and aminoluciferin, well known substrates of firefly luciferase, are environment-sensitive fluorophores with unusual and still-unexploited properties. Both fluorophores show strong solvatochromism. Moreover, luciferin fluorescence is influenced by pH and water abundance. These features allow to detect local variations of pH, solvent polarity and local water concentration, even when they occur simultaneously, by analyzing excitation and emission spectra. Here, we describe the characterization of (amino)luciferin-labeled derivatives of four bioactive peptides: the antimicrobial peptides GKY20 and ApoB_L, the antitumor peptide p53pAnt and the integrin-binding peptide RGD. The two probes allowed for the study of the interaction of the peptides with model membranes, SDS micelles, lipopolysaccharide micelles and Escherichia coli cells. K_d values and binding stoichiometries for lipopolysaccharide were also determined. Aminoluciferin also proved to be very well-suited to confocal laser scanning microscopy. Overall, the characterization of the labeled peptides demonstrates that luciferin and aminoluciferin are previously neglected environment-sensitive labels with widespread potential applications in the study of proteins and peptides. Full article

(This article belongs to the Special Issue Synthetic Peptides and Peptidomimetics: From Basic Science to Biomedical Applications)

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17 pages, 1408 KiB

Open AccessArticle

Anti-Cancer Effects of Cyclic Peptide ALOS4 in a Human Melanoma Mouse Model

by Bar Levi, Shiri Yacobovich, Michael Kirby, Maria Becker, Oryan Agranyoni, Boris Redko, Gary Gellerman, Albert Pinhasov, Igor Koman and Elimelech Nesher

Int. J. Mol. Sci. 2021, 22(17), 9579; https://doi.org/10.3390/ijms22179579 - 3 Sep 2021

Cited by 6 | Viewed by 2635

Abstract

We examined the effects of ALOS4, a cyclic peptide discovered previously by phage library selection against integrin α_vβ₃, on a human melanoma (A375) xenograft model to determine its abilities as a potential anti-cancer agent. We found that ALOS4 promoted healthy weight gain in A375-engrafted nude mice and reduced melanoma tumor mass and volume. Despite these positive changes, examination of the tumor tissue did not indicate any significant effects on proliferation, mitotic index, tissue vascularization, or reduction of αSMA or Ki-67 tumor markers. Modulation in overall expression of critical downstream α_vβ₃ integrin factors, such as FAK and Src, as well as reductions in gene expression of c-Fos and c-Jun transcription factors, indirectly confirmed our suspicions that ALOS4 is likely acting through an integrin-mediated pathway. Further, we found no overt formulation issues with ALOS4 regarding interaction with standard inert laboratory materials (polypropylene, borosilicate glass) or with pH and temperature stability under prolonged storage. Collectively, ALOS4 appears to be safe, chemically stable, and produces anti-cancer effects in a human xenograft model of melanoma. We believe these results suggest a role for ALOS4 in an integrin-mediated pathway in exerting its anti-cancer effects possibly through immune response modulation. Full article

(This article belongs to the Special Issue Synthetic Peptides and Peptidomimetics: From Basic Science to Biomedical Applications)

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14 pages, 1861 KiB

Open AccessArticle

Peptide Derivatives of the Zonulin Inhibitor Larazotide (AT1001) as Potential Anti SARS-CoV-2: Molecular Modelling, Synthesis and Bioactivity Evaluation

by Simone Di Micco, Simona Musella, Marina Sala, Maria C. Scala, Graciela Andrei, Robert Snoeck, Giuseppe Bifulco, Pietro Campiglia and Alessio Fasano

Int. J. Mol. Sci. 2021, 22(17), 9427; https://doi.org/10.3390/ijms22179427 - 30 Aug 2021

Cited by 14 | Viewed by 3803

Abstract

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been identified as the pathogen responsible for the outbreak of a severe, rapidly developing pneumonia (Coronavirus disease 2019, COVID-19). The virus enzyme, called 3CLpro or main protease (M^pro), is essential for viral replication, making it a most promising target for antiviral drug development. Recently, we adopted the drug repurposing as appropriate strategy to give fast response to global COVID-19 epidemic, by demonstrating that the zonulin octapeptide inhibitor AT1001 (Larazotide acetate) binds M^pro catalytic domain. Thus, in the present study we tried to investigate the antiviral activity of AT1001, along with five derivatives, by cell-based assays. Our results provide with the identification of AT1001 peptide molecular framework for lead optimization step to develop new generations of antiviral agents of SARS-CoV-2 with an improved biological activity, expanding the chance for success in clinical trials. Full article

(This article belongs to the Special Issue Synthetic Peptides and Peptidomimetics: From Basic Science to Biomedical Applications)

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16 pages, 3258 KiB

Open AccessArticle

[⁶⁸Ga]Ga-DFO-c(RGDyK): Synthesis and Evaluation of Its Potential for Tumor Imaging in Mice

by Sona Krajcovicova, Andrea Daniskova, Katerina Bendova, Zbynek Novy, Miroslav Soural and Milos Petrik

Int. J. Mol. Sci. 2021, 22(14), 7391; https://doi.org/10.3390/ijms22147391 - 9 Jul 2021

Cited by 2 | Viewed by 2937

Abstract

Angiogenesis has a pivotal role in tumor growth and the metastatic process. Molecular imaging was shown to be useful for imaging of tumor-induced angiogenesis. A great variety of radiolabeled peptides have been developed to target αvβ3 integrin, a target structure involved in the tumor-induced angiogenic process. The presented study aimed to synthesize deferoxamine (DFO)-based c(RGD) peptide conjugate for radiolabeling with gallium-68 and perform its basic preclinical characterization including testing of its tumor-imaging potential. DFO-c(RGDyK) was labeled with gallium-68 with high radiochemical purity. In vitro characterization including stability, partition coefficient, protein binding determination, tumor cell uptake assays, and ex vivo biodistribution as well as PET/CT imaging was performed. [⁶⁸Ga]Ga-DFO-c(RGDyK) showed hydrophilic properties, high stability in PBS and human serum, and specific uptake in U-87 MG and M21 tumor cell lines in vitro and in vivo. We have shown here that [⁶⁸Ga]Ga-DFO-c(RGDyK) can be used for αvβ3 integrin targeting, allowing imaging of tumor-induced angiogenesis by positron emission tomography. Full article

(This article belongs to the Special Issue Synthetic Peptides and Peptidomimetics: From Basic Science to Biomedical Applications)

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14 pages, 2350 KiB

Open AccessArticle

X-ray Crystallographic Structure of α-Helical Peptide Stabilized by Hydrocarbon Stapling at i,i + 1 Positions

by Yui Makura, Atsushi Ueda, Takuma Kato, Akihiro Iyoshi, Mei Higuchi, Mitsunobu Doi and Masakazu Tanaka

Int. J. Mol. Sci. 2021, 22(10), 5364; https://doi.org/10.3390/ijms22105364 - 19 May 2021

Cited by 3 | Viewed by 2757

Abstract

Hydrocarbon stapling is a useful tool for stabilizing the secondary structure of peptides. Among several methods, hydrocarbon stapling at i,i + 1 positions was not extensively studied, and their secondary structures are not clarified. In this study, we investigate i,i + 1 hydrocarbon stapling between cis-4-allyloxy-l-proline and various olefin-tethered amino acids. Depending on the ring size of the stapled side chains and structure of the olefin-tethered amino acids, E- or Z-selectivities were observed during the ring-closing metathesis reaction (E/Z was up to 8.5:1 for 17–14-membered rings and up to 1:20 for 13-membered rings). We performed X-ray crystallographic analysis of hydrocarbon stapled peptide at i,i + 1 positions. The X-ray crystallographic structure suggested that the i,i + 1 staple stabilizes the peptide secondary structure to the right-handed α-helix. These findings are especially important for short oligopeptides because the employed stapling method uses two minimal amino acid residues adjacent to each other. Full article

(This article belongs to the Special Issue Synthetic Peptides and Peptidomimetics: From Basic Science to Biomedical Applications)

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3 pages, 632 KiB

Open AccessArticle

Novel Cell Permeable Polymers of N-Substituted L-2,3-Diaminopropionic Acid (DAPEGs) and Cellular Consequences of Their Interactions with Nucleic Acids

by Anita Romanowska, Katarzyna Węgrzyn, Katarzyna Bury, Emilia Sikorska, Aleksandra Gnatek, Agnieszka Piwkowska, Igor Konieczny, Adam Lesner and Magdalena Wysocka

Int. J. Mol. Sci. 2021, 22(5), 2571; https://doi.org/10.3390/ijms22052571 - 4 Mar 2021

Cited by 1 | Viewed by 2488

Abstract

The present study aimed to synthesize novel polycationic polymers composed of N-substituted L-2,3-diaminopropionic acid residues (DAPEGs) and investigate their cell permeability, cytotoxicity, and DNA-binding ability. The most efficient cell membrane-penetrating compounds (O2Oc-Dap(GO2)_n-O2Oc-NH₂, where n = 4, 6, and 8) showed dsDNA binding with a binding constant in the micromolar range (0.3, 3.4, and 0.19 µM, respectively) and were not cytotoxic to HB2 and MDA-MB-231 cells. Selected compounds used in the transfection of a GFP plasmid showed high transfection efficacy and minimal cytotoxicity. Their interaction with plasmid DNA and the increasing length of the main chain of tested compounds strongly influenced the organization and shape of the flower-like nanostructures formed, which were unique for 5/6-FAM-O2Oc-[Dap(GO2)]₈-O2Oc-NH₂ and typical for large proteins. Full article

(This article belongs to the Special Issue Synthetic Peptides and Peptidomimetics: From Basic Science to Biomedical Applications)

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Review

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20 pages, 2061 KiB

Open AccessReview

Multitalented Synthetic Antimicrobial Peptides and Their Antibacterial, Antifungal and Antiviral Mechanisms

by Tania Vanzolini, Michela Bruschi, Andrea C. Rinaldi, Mauro Magnani and Alessandra Fraternale

Int. J. Mol. Sci. 2022, 23(1), 545; https://doi.org/10.3390/ijms23010545 - 4 Jan 2022

Cited by 55 | Viewed by 6920

Abstract

Despite the great strides in healthcare during the last century, some challenges still remained unanswered. The development of multi-drug resistant bacteria, the alarming growth of fungal infections, the emerging/re-emerging of viral diseases are yet a worldwide threat. Since the discovery of natural antimicrobial peptides able to broadly hit several pathogens, peptide-based therapeutics have been under the lenses of the researchers. This review aims to focus on synthetic peptides and elucidate their multifaceted mechanisms of action as antiviral, antibacterial and antifungal agents. Antimicrobial peptides generally affect highly preserved structures, e.g., the phospholipid membrane via pore formation or other constitutive targets like peptidoglycans in Gram-negative and Gram-positive bacteria, and glucan in the fungal cell wall. Additionally, some peptides are particularly active on biofilm destabilizing the microbial communities. They can also act intracellularly, e.g., on protein biosynthesis or DNA replication. Their intracellular properties are extended upon viral infection since peptides can influence several steps along the virus life cycle starting from viral receptor-cell interaction to the budding. Besides their mode of action, improvements in manufacturing to increase their half-life and performances are also taken into consideration together with advantages and impairments in the clinical usage. Thus far, the progress of new synthetic peptide-based approaches is making them a promising tool to counteract emerging infections. Full article

(This article belongs to the Special Issue Synthetic Peptides and Peptidomimetics: From Basic Science to Biomedical Applications)

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31 pages, 7085 KiB

Open AccessReview

Peptide-Assisted Nucleic Acid Delivery Systems on the Rise

by Shabnam Tarvirdipour, Michal Skowicki, Cora-Ann Schoenenberger and Cornelia G. Palivan

Int. J. Mol. Sci. 2021, 22(16), 9092; https://doi.org/10.3390/ijms22169092 - 23 Aug 2021

Cited by 12 | Viewed by 5849

Abstract

Concerns associated with nanocarriers’ therapeutic efficacy and side effects have led to the development of strategies to advance them into targeted and responsive delivery systems. Owing to their bioactivity and biocompatibility, peptides play a key role in these strategies and, thus, have been extensively studied in nanomedicine. Peptide-based nanocarriers, in particular, have burgeoned with advances in purely peptidic structures and in combinations of peptides, both native and modified, with polymers, lipids, and inorganic nanoparticles. In this review, we summarize advances on peptides promoting gene delivery systems. The efficacy of nucleic acid therapies largely depends on cell internalization and the delivery to subcellular organelles. Hence, the review focuses on nanocarriers where peptides are pivotal in ferrying nucleic acids to their site of action, with a special emphasis on peptides that assist anionic, water-soluble nucleic acids in crossing the membrane barriers they encounter on their way to efficient function. In a second part, we address how peptides advance nanoassembly delivery tools, such that they navigate delivery barriers and release their nucleic acid cargo at specific sites in a controlled fashion. Full article

(This article belongs to the Special Issue Synthetic Peptides and Peptidomimetics: From Basic Science to Biomedical Applications)

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22 pages, 2941 KiB

Open AccessReview

Role of Peptides in Diagnostics

by Shashank Pandey, Gaurav Malviya and Magdalena Chottova Dvorakova

Int. J. Mol. Sci. 2021, 22(16), 8828; https://doi.org/10.3390/ijms22168828 - 17 Aug 2021

Cited by 43 | Viewed by 5514

Abstract

The specificity of a diagnostic assay depends upon the purity of the biomolecules used as a probe. To get specific and accurate information of a disease, the use of synthetic peptides in diagnostics have increased in the last few decades, because of their high purity profile and ability to get modified chemically. The discovered peptide probes are used either in imaging diagnostics or in non-imaging diagnostics. In non-imaging diagnostics, techniques such as Enzyme-Linked Immunosorbent Assay (ELISA), lateral flow devices (i.e., point-of-care testing), or microarray or LC-MS/MS are used for direct analysis of biofluids. Among all, peptide-based ELISA is considered to be the most preferred technology platform. Similarly, peptides can also be used as probes for imaging techniques, such as single-photon emission computed tomography (SPECT) and positron emission tomography (PET). The role of radiolabeled peptides, such as somatostatin receptors, interleukin 2 receptor, prostate specific membrane antigen, αβ3 integrin receptor, gastrin-releasing peptide, chemokine receptor 4, and urokinase-type plasminogen receptor, are well established tools for targeted molecular imaging ortumor receptor imaging. Low molecular weight peptides allow a rapid clearance from the blood and result in favorable target-to-non-target ratios. It also displays a good tissue penetration and non-immunogenicity. The only drawback of using peptides is their potential low metabolic stability. In this review article, we have discussed and evaluated the role of peptides in imaging and non-imaging diagnostics. The most popular non-imaging and imaging diagnostic platforms are discussed, categorized, and ranked, as per their scientific contribution on PUBMED. Moreover, the applicability of peptide-based diagnostics in deadly diseases, mainly COVID-19 and cancer, is also discussed in detail. Full article

(This article belongs to the Special Issue Synthetic Peptides and Peptidomimetics: From Basic Science to Biomedical Applications)

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23 pages, 2827 KiB

Open AccessReview

Recent Applications of Retro-Inverso Peptides

by Nunzianna Doti, Mario Mardirossian, Annamaria Sandomenico, Menotti Ruvo and Andrea Caporale

Int. J. Mol. Sci. 2021, 22(16), 8677; https://doi.org/10.3390/ijms22168677 - 12 Aug 2021

Cited by 41 | Viewed by 4675

Abstract

Natural and de novo designed peptides are gaining an ever-growing interest as drugs against several diseases. Their use is however limited by the intrinsic low bioavailability and poor stability. To overcome these issues retro-inverso analogues have been investigated for decades as more stable surrogates of peptides composed of natural amino acids. Retro-inverso peptides possess reversed sequences and chirality compared to the parent molecules maintaining at the same time an identical array of side chains and in some cases similar structure. The inverted chirality renders them less prone to degradation by endogenous proteases conferring enhanced half-lives and an increased potential as new drugs. However, given their general incapability to adopt the 3D structure of the parent peptides their application should be careful evaluated and investigated case by case. Here, we review the application of retro-inverso peptides in anticancer therapies, in immunology, in neurodegenerative diseases, and as antimicrobials, analyzing pros and cons of this interesting subclass of molecules. Full article

(This article belongs to the Special Issue Synthetic Peptides and Peptidomimetics: From Basic Science to Biomedical Applications)

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