E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Special Issue "Ribosome-Inactivating Proteins--Commemorative Issue in Honor of Professor Fiorenzo Stirpe"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Bioorganic Chemistry".

Deadline for manuscript submissions: closed (30 September 2016)

Special Issue Editor

Guest Editor
Prof. Dr. Els Van Damme

Ghent University, Belgium
Website | E-Mail
Interests: lectins; carbohydrate-binding proteins; protein-carbohydrate interactions; carbohydrate recognition; glycosylation; biological activity; ribosome inactivating proteins; toxin domain; physiological importance; defense and immunity; stress proteins; glycobiology

Special Issue Information

Dear Colleagues,

Ever since the discovery of the first ribosome-inactivating protein, this group of plant toxins has received a lot of attention from researchers in various disciplines. Ribosome-inactivating proteins have been studied in detail for their distribution in nature, their molecular structure and toxicity, and have been proven as valuable tools in cancer research. Despite the long history of these proteins, new ribosome-inactivating proteins are still being discovered in plants and, recently, also in other kingdoms of life. Current research mainly focuses on the physiological importance of ribosome-inactivating proteins for plant growth and development, as well as their applications in agricultural and medical research.

Fiorenzo Stirpe is Professor Emeritus at the Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy. He is (co)author of over 280 publications in international journals and several book chapters. Prof. Stirpe is co-editor of one book entitled ‘Ribosome-Inactivating Proteins—Ricin and Related Proteins’. Furthermore, he is holder of 10 patents related to the applicability of ribosome-inactivating proteins and immunotoxins. For his pioneering work related to the study of plant toxins and the preparation of immunotoxins he was offered some prestigious awards and his work has been highly cited (h-index 55) by researchers from various disciplines.

In honor of Professor Fiorenzo Stirpe for his outstanding contribution to research on plant toxins, this commemorative issue of Molecules welcomes submission of previously unpublished manuscripts from original work or reviews on ‘Ribosome-Inactivating Proteins’. We plan to receive submissions from 15 April to 30 September 2016.

Prof. Dr. Els Van Damme
Guest Editor

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 papers will be 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. Molecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). 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

  • Abrin
  • immunotoxin
  • N-glycosidase activity
  • plant toxin
  • Ribosome-inactivating protein
  • RIP
  • Ricin
  • RNA binding protein

Published Papers (9 papers)

View options order results:
result details:
Displaying articles 1-9
Export citation of selected articles as:

Editorial

Jump to: Research, Review

Open AccessEditorial Special Issue: Ribosome-Inactivating Proteins—Commemorative Issue in Honor of Professor Fiorenzo Stirpe
Molecules 2017, 22(2), 316; doi:10.3390/molecules22020316
Received: 15 February 2017 / Revised: 16 February 2017 / Accepted: 16 February 2017 / Published: 18 February 2017
PDF Full-text (143 KB) | HTML Full-text | XML Full-text
Abstract
The family of ribosome-inactivating proteins (RIPs) groups all enzymes (EC.3.2.2.22) with a so-called RIP domain which comprises N-glycosidase activity and enables these proteins to catalytically inactivate ribosomes.[...] Full article

Research

Jump to: Editorial, Review

Open AccessArticle Lectin Digestibility and Stability of Elderberry Antioxidants to Heat Treatment In Vitro
Molecules 2017, 22(1), 95; doi:10.3390/molecules22010095
Received: 4 October 2016 / Revised: 18 December 2016 / Accepted: 29 December 2016 / Published: 6 January 2017
Cited by 1 | PDF Full-text (2071 KB) | HTML Full-text | XML Full-text
Abstract
Elderberry contains healthy low molecular weight nutraceuticals and lectins which are sequence-related to the elderberry allergen Sam n1. Some of these lectins are type II ribosome-inactivating proteins. The sensitivity of native lectins present in elderberry fruits and bark to the proteolysis triggered by
[...] Read more.
Elderberry contains healthy low molecular weight nutraceuticals and lectins which are sequence-related to the elderberry allergen Sam n1. Some of these lectins are type II ribosome-inactivating proteins. The sensitivity of native lectins present in elderberry fruits and bark to the proteolysis triggered by in vitro simulated gastric and duodenal fluids has been investigated. It was found that these lectins are refractory to proteolysis. Nonetheless, incubation for 5–10 min in a boiling water bath completely sensitized them to the hydrolytic enzymes in vitro. Under these conditions neither total Folin-Ciocalteau’s reagent reactive compounds, total anthocyanins and the mixture of cyanidin-3-glucoside plus cyanidin-3-sambubioside, nor antioxidant and free-radical scavenging activities were affected by more than 10% for incubations of up to 20 min. Therefore, short-time heat treatment reduces potential allergy-related risks deriving from elderberry consumption without seriously affecting its properties as an antioxidant and free-radical scavenging food. Full article
Figures

Figure 1

Open AccessArticle DeBouganin Diabody Fusion Protein Overcomes Drug Resistance to ADCs Comprised of Anti-Microtubule Agents
Molecules 2016, 21(12), 1741; doi:10.3390/molecules21121741
Received: 15 October 2016 / Revised: 9 December 2016 / Accepted: 12 December 2016 / Published: 17 December 2016
Cited by 2 | PDF Full-text (1974 KB) | HTML Full-text | XML Full-text
Abstract
Antibody drug conjugates (ADC), comprised of highly potent small molecule payloads chemically conjugated to a full-length antibody, represent a growing class of therapeutic agents. The targeting of cytotoxic payloads via the specificity and selectivity of the antibody has led to substantial clinical benefits.
[...] Read more.
Antibody drug conjugates (ADC), comprised of highly potent small molecule payloads chemically conjugated to a full-length antibody, represent a growing class of therapeutic agents. The targeting of cytotoxic payloads via the specificity and selectivity of the antibody has led to substantial clinical benefits. However, ADC potency can be altered by mechanisms of resistance such as overexpression of efflux pumps or anti-apoptotic proteins. DeBouganin is a de-immunized variant of bouganin, a ribosome-inactivating protein (RIP) that blocks protein synthesis, thereby leading to apoptosis. When conjugated to trastuzumab (T-deB), deBouganin was more potent than ado-trastuzumab-emtansine (T-DM1) and unaffected by resistance mechanisms to which DM1 is susceptible. To further highlight the differentiating mechanism of action of deBouganin, HCC1419 and BT-474 tumor cells that survived T-DM1 or trastuzumab-MMAE (T-MMAE) treatment were treated with an anti-HER2 C6.5 diabody–deBouganin fusion protein or T-deB. C6.5 diabody–deBouganin and T-deB were potent against HCC1419 and BT-474 cells that were resistant to T-DM1 or T-MMAE killing. The resistant phenotype involved MDR pumps, Bcl-2 family members, and the presence of additional unknown pathways. Overall, the data suggest that deBouganin is effective against tumor cell resistance mechanisms selected in response to ADCs composed of anti-microtubule payloads. Full article
Figures

Figure 1

Open AccessArticle Mono-PEGylation of Alpha-MMC and MAP30 from Momordica charantia L.: Production, Identification and Anti-Tumor Activity
Molecules 2016, 21(11), 1457; doi:10.3390/molecules21111457
Received: 20 September 2016 / Revised: 29 October 2016 / Accepted: 29 October 2016 / Published: 31 October 2016
Cited by 2 | PDF Full-text (2638 KB) | HTML Full-text | XML Full-text
Abstract
PEGylation is a well-established and effective strategy to decrease immunogenicity, which can increase the stability and in vivo half-life time. However, the generation of multi-site modified products is inevitable due to the lysine chemistry, which will bring difficulties in subsequent research, such as
[...] Read more.
PEGylation is a well-established and effective strategy to decrease immunogenicity, which can increase the stability and in vivo half-life time. However, the generation of multi-site modified products is inevitable due to the lysine chemistry, which will bring difficulties in subsequent research, such as purification and quantification. Site-specific modification by mPEG-succinimidyl carbonate (mPEG-SC) is a widely used method for N-terminal conjugation. In this study, we used it for site-directed modification on two ribosome-inactivating proteins (RIPs), alpha-momorcharin (α-MMC) and momordica anti-HIV protein (MAP30), from Momordica charantia L. According to the optimization of previous modification conditions, we compared Macro-Cap SP with SP-Sepharose FF chromatography for separating the final mPEGylated RIPs. Two kinds of methods both can obtain homogenous mPEGylated RIPs which were identified by sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE), isoelectric focusing electrophoresis (IEF), and matrix-assisted laser desorption ionization-time of flight/time of flight (MALDI-TOF/TOF) analysis. We also used iodine staining method to detect the amount of unmodified PEG. Furthermore, the inhibition activity of both mPEGylated and non-PEGylated RIPs against human lung adenocarcinoma epithelial A549 cells was detected. All of the results suggested that the mPEGylated α-MMC/MAP30 might be potentially developed as new anti-tumor drugs. Full article
Figures

Figure 1

Open AccessArticle Ribosome Inactivating Proteins from Rosaceae
Molecules 2016, 21(8), 1105; doi:10.3390/molecules21081105
Received: 11 July 2016 / Revised: 16 August 2016 / Accepted: 18 August 2016 / Published: 22 August 2016
Cited by 6 | PDF Full-text (3948 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ribosome-inactivating proteins (RIPs) are widespread among higher plants of different taxonomic orders. In this study, we report on the RIP sequences found in the genome/transcriptome of several important Rosaceae species, including many economically important edible fruits such as apple, pear, peach, apricot, and
[...] Read more.
Ribosome-inactivating proteins (RIPs) are widespread among higher plants of different taxonomic orders. In this study, we report on the RIP sequences found in the genome/transcriptome of several important Rosaceae species, including many economically important edible fruits such as apple, pear, peach, apricot, and strawberry. All RIP domains from Rosaceae share high sequence similarity with conserved residues in the catalytic site and the carbohydrate binding sites. The genomes of Malus domestica and Pyrus communis contain both type 1 and type 2 RIP sequences, whereas for Prunus mume, Prunus persica, Pyrus bretschneideri, and Pyrus communis a complex set of type 1 RIP sequences was retrieved. Heterologous expression and purification of the type 1 as well as the type 2 RIP from apple allowed to characterize the biological activity of the proteins. Both RIPs from Malus domestica can inhibit protein synthesis. Furthermore, molecular modelling suggests that RIPs from Rosaceae possess three-dimensional structures that are highly similar to the model proteins and can bind to RIP substrates. Screening of the recombinant type 2 RIP from apple on a glycan array revealed that this type 2 RIP interacts with terminal sialic acid residues. Our data suggest that the RIPs from Rosaceae are biologically active proteins. Full article
Figures

Figure 1

Review

Jump to: Editorial, Research

Open AccessReview Hyperuricaemia, Xanthine Oxidoreductase and Ribosome‐Inactivating Proteins from Plants: The Contributions of Fiorenzo Stirpe to Frontline Research
Molecules 2017, 22(2), 206; doi:10.3390/molecules22020206
Received: 30 December 2016 / Revised: 16 January 2017 / Accepted: 23 January 2017 / Published: 27 January 2017
Cited by 1 | PDF Full-text (247 KB) | HTML Full-text | XML Full-text
Abstract
The enzymes called ribosome‐inactivating proteins (RIPs) that are able to depurinate nucleic acids and arrest vital cellular functions, including protein synthesis, are still a frontline research field, mostly because of their promising medical applications. The contributions of Stirpe to the development of these
[...] Read more.
The enzymes called ribosome‐inactivating proteins (RIPs) that are able to depurinate nucleic acids and arrest vital cellular functions, including protein synthesis, are still a frontline research field, mostly because of their promising medical applications. The contributions of Stirpe to the development of these studies has been one of the most relevant. After a short biographical introduction, an overview is offered of the main results obtained by his investigations during last 55 years on his main research lines: hyperuricaemia, xanthine oxidoreductase and RIPs. Full article
Open AccessReview Ribosome-Inactivating Proteins from Plants: A Historical Overview
Molecules 2016, 21(12), 1627; doi:10.3390/molecules21121627
Received: 7 November 2016 / Revised: 22 November 2016 / Accepted: 23 November 2016 / Published: 26 November 2016
Cited by 10 | PDF Full-text (816 KB) | HTML Full-text | XML Full-text
Abstract
This review provides a historical overview of the research on plant ribosome-inactivating proteins (RIPs), starting from the first studies at the end of eighteenth century involving the purification of abrin and ricin, as well as the immunological experiments of Paul Erlich. Interest in
[...] Read more.
This review provides a historical overview of the research on plant ribosome-inactivating proteins (RIPs), starting from the first studies at the end of eighteenth century involving the purification of abrin and ricin, as well as the immunological experiments of Paul Erlich. Interest in these plant toxins was revived in 1970 by the observation of their anticancer activity, which has given rise to a large amount of research contributing to the development of various scientific fields. Biochemistry analyses succeeded in identifying the enzymatic activity of RIPs and allowed for a better understanding of the ribosomal machinery. Studies on RIP/cell interactions were able to detail the endocytosis and intracellular routing of ricin, thus increasing our knowledge of how cells handle exogenous proteins. The identification of new RIPs and the finding that most RIPs are single-chain polypeptides, together with their genetic sequencing, has aided in the development of new phylogenetic theories. Overall, the biological properties of these proteins, including their abortifacient, anticancer, antiviral and neurotoxic activities, suggest that RIPs could be utilized in agriculture and in many biomedical fields, including clinical drug development. Full article
Figures

Figure 1

Open AccessReview Structures and Ribosomal Interaction of Ribosome-Inactivating Proteins
Molecules 2016, 21(11), 1588; doi:10.3390/molecules21111588
Received: 10 October 2016 / Revised: 9 November 2016 / Accepted: 15 November 2016 / Published: 21 November 2016
Cited by 4 | PDF Full-text (3993 KB) | HTML Full-text | XML Full-text
Abstract
Ribosome-inactivating proteins (RIPs) including ricin, Shiga toxin, and trichosanthin, are RNA N-glycosidases that depurinate a specific adenine residue (A-4324 in rat 28S ribosomal RNA, rRNA) in the conserved α-sarcin/ricin loop (α-SRL) of rRNA. RIPs are grouped into three types according to the
[...] Read more.
Ribosome-inactivating proteins (RIPs) including ricin, Shiga toxin, and trichosanthin, are RNA N-glycosidases that depurinate a specific adenine residue (A-4324 in rat 28S ribosomal RNA, rRNA) in the conserved α-sarcin/ricin loop (α-SRL) of rRNA. RIPs are grouped into three types according to the number of subunits and the organization of the precursor sequences. RIPs are two-domain proteins, with the active site located in the cleft between the N- and C-terminal domains. It has been found that the basic surface residues of the RIPs promote rapid and specific targeting to the ribosome and a number of RIPs have been shown to interact with the C-terminal regions of the P proteins of the ribosome. At present, the structural basis for the interaction of trichosanthin and ricin-A chain toward P2 peptide is known. This review surveys the structural features of the representative RIPs and discusses how they approach and interact with the ribosome. Full article
Figures

Figure 1

Open AccessReview Plants Producing Ribosome-Inactivating Proteins in Traditional Medicine
Molecules 2016, 21(11), 1560; doi:10.3390/molecules21111560
Received: 3 October 2016 / Revised: 4 November 2016 / Accepted: 9 November 2016 / Published: 18 November 2016
Cited by 5 | PDF Full-text (289 KB) | HTML Full-text | XML Full-text
Abstract
Ribosome-inactivating proteins (RIPs) are enzymes that deadenylate nucleic acids and are broadly distributed in the plant kingdom. Many plants that contain RIPs are listed in the pharmacopoeias of folk medicine all over the world, mostly because of their toxicity. This review analyses the
[...] Read more.
Ribosome-inactivating proteins (RIPs) are enzymes that deadenylate nucleic acids and are broadly distributed in the plant kingdom. Many plants that contain RIPs are listed in the pharmacopoeias of folk medicine all over the world, mostly because of their toxicity. This review analyses the position occupied in traditional medicine by plants from which RIPs have been isolated. The overview starts from the antique age of the Mediterranean area with ancient Egypt, followed by the Greek and Roman classic period. Then, the ancient oriental civilizations of China and India are evaluated. More recently, Unani medicine and European folk medicine are examined. Finally, the African and American folk medicines are taken into consideration. In conclusion, a list of RIP-expressing plants, which have been used in folk medicine, is provided with the geographical distribution and the prescriptions that are recommended by traditional healers. Some final considerations are provided on the present utilization of such herbal treatments, both in developing and developed countries, often in the absence of scientific validation. The most promising prospect for the medicinal use of RIP-expressing plants is the conjugation of purified RIPs to antibodies that recognise tumour antigens for cancer therapy. Full article
Back to Top