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ISSN (Print): 0929-8665
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Special Issue Submission
"Protein and Peptide Letters provides an excellent venue for communication of succinct reports of interesting research findings."
Jeffrey J. Gorman
Institute of Molecular Bioscience, Australia
Renin-Angiotensin System: Role in cerebrovascular, neurodegenerative and psychiatric disease
Guest Editor(s): Lucas M. Kangussu
Tentative Publication Date: August, 2019
Submit Abstract via Email
Organic-Inorganic Hybrid Materials and Their Applications
Guest Editor(s): Kin-ya Tomizaki, Yoshio Hamada, Kenji Usui
It was a great experience working with Bentham Science Publishers. The reviews were fair, prompt and the suggestions given made us analyze our work more deeply and unearth important issues and their solutions.
The proof-reading process of Bentham Science was also prompt and author-friendly. They took utmost care to ensure that all of our concerns were addressed in the final published form of the paper. The discounts offered to authors were also most appreciated.
The fast communication and periodical updates made us submit another research paper to Bentham Science Publishers in their journal, Current Bioinformatics, which is currently under review
Thank you Bentham Science Publishers!
Assistant Professor. Shomona GJ (Department of CSE, SSN College of Engineering, Chenniai, India)
13 Abstract Ahead of Print are available electronically
21 Articles Ahead of Print are available electronically
A wide range of solvent accessibility methods to investigate structural features and conformational changes of macro-molecules in
solution are described in the articles in this issue. These methods have grown substantially of the past few decades, and are highly
complementary to other more widely used structural elucidation techniques for biological macromolecules, such as x-ray diffraction, cryoelectron
microscopy, and nuclear magnetic resonance. While these more widely known methods are all excellent techniques for studying
protein structure, they often require protein engineering, high concentrations of sample, or non-physiological sample environments, and in
addition, can be limited by the size and/or complexity of the molecule. Solvent accessibility methods have their own unique advantages and
disadvantages, and are increasingly used as stand-alone methods or as part of a suite of tools to characterize macromolecules.
The concept of footprinting refers to the method of delineating interactions between macromolecules, i.e., the "footprint" of one molecule
on another. Some of the earliest footprinting methods used enzymatic digestion to define the areas on nucleic acid which were solvent
protected by binding partners, i.e., a protein protected a specific region on the nucleic acid from digestion, thereby delineating a "footprint" on
the nucleic acid . Chemical methods for determining solvent accessibility, such as methylation, were developed around the same time, and
had the advantage of using a smaller probe, thus yielding higher resolution footprints. Many variations on enzymatic and chemical
footprinting for both nucleic acid and proteins have been developed in the last several decades. Protein footprinting in particular, has
historically been deployed using proteases  and antibodies  as well as other modification methods such as hydroxyl radical footprinting
using reagents . More recently, hydroxyl radical footprinting has been developed using an external energy source for the generation of
hydroxyl radicals, as in electron , laser-induced , X-ray [7, 8], and very recently, plasma-induced radical formation . The hydroxyl
radical, in particular, is an excellent probe for determining protein-protein and protein-nucleic acid interactions, because of its small size and
high reactivity. The method is variously referred to as Radical Probe Mass Spectrometry (RP-MS), Hydroxyl Radical Footprinting (HRF),
Fast Photochemical Oxidative Footprinting (FPOP), X-ray Footprinting (XRF), or X-ray Footrpinting with Mass Spectrometry (XF-MS)
depending on the radical source and method.
In this thematic issue, the first review article is by Maleknia & Downard and covers the development of RP-MS over the last two decades,
describing the technological advances of the different methods of hydroxyl generation through the years. In contrast to the hydroxyl radical
reaction with protein sidechains, the method of Hydrogen Exchange Mass Spectrometry (HDX-MS), as described in the second review by
Benhaim et al., relies on the modification of protein backbone amide groups. This method is well-developed, increasingly used in industrial
applications, and provides a natural complement to the other side-chain labeling footprinting methods described in this issue. FPOP is
reviewed by Shi & Gross, and describes the recent development of a lab-based radical generating method using an excimer laser to induce
radical formation. A review by Garcia et al., then describes the application of the method for characterization of biotherapeutics. Specific
applications to membrane proteins are described in the review by Gupta, while Bohon describes the history of the development of an X-ray
footprinting beamline at the Brookhaven National Laboratory on the East Coast of the United States.
In the research article section, Leser et al., describe a novel approach for oxidative footprinting, a "lab on a chip" method which enables
many different chemical environments to be probed quickly and simultaneously, and will be of particular interest for biotechnology
applications. Morton et al., describe the new development of an X-ray footprinting beamline at Lawrence Berkeley national Laboratory on the
West Coast of the United States.
The primary aim is to cover the most exciting and promising new areas of research in peptide science as
applied to therapeutic discovery and development. The strengths of peptides as drug targets are their high
potency, specificity and good safety profile. These positive attributes of peptides along with advances in
drug delivery technologies have afforded a renewed interest in the discovery, optimization and
development of peptides as therapeutics. In this themed issue, the most compelling indications and targets
for peptide therapeutics are reviewed and discussed with the intent to demonstrate that peptides have
broad applicability in many therapeutic areas. Target selection for peptide therapeutics is challenging due
to the inherent properties of peptides. Therefore, identifying a clear differentiation strategy for a new
peptide program over a small molecule or antibody program from the outset is critical for successful
navigation of drug development hurdles. The latest techniques for overcoming some of the perceived
limitations of peptides to increase their druggability will be reviewed and discussed. Emerging
technologies for stabilizing peptides for sufficient in vivo half-life will be described and evaluated, as
well as novel technologies for getting peptides across cell membranes to reach intracellular targets and
across the blood brain barrier to reach central nervous system targets. Capitalizing on the strengths of
peptides in this issue, the latest advancements in therapeutic peptidic hormones, peptides targeting
protein-protein interactions especially for oncology indications, venom peptides as therapeutics as well as
diagnostics, and antimicrobial peptide progress will be covered with emphasis on the distinctive
properties peptides have compared to other therapeutics.
Proteins are the material basis of life, and the basic organic matter that constitutes cells. In cells, proteins are the principal
catalytic agents, structural elements, signal transmitters, transporters and molecular machines. But individual proteins do not
function alone, they must interact with other molecules, such as proteins, RNAs, DNAs and small molecule compounds, to
carry out their cellular roles.
Studying these interactions has very important biological implications. Typically, interactions of proteins are identified and
characterized by a number of biochemical or biophysical experimental methods. Although these experiments are very valuable
and contribute significantly to our understanding of the mechanisms of protein interactions, technical challenges make these
experiments both labor intensive and time consuming. Therefore, reliable computational methods are more and more widely
recognized by researchers.
In recent years, computational techniques have been successfully applied to predict the interactions between protein and
various kinds of molecules. Especially, protein–protein interactions prediction, protein–RNA interactions prediction and
protein–drug interactions prediction based on heterogeneous biological data have become critical topics in the search of
functions of proteins and therapeutic targets for various diseases. With the development and application of many new
computational techniques, such as machine learning, deep learning, new feature extraction methods and network methods, a
great progress has been made in the field of protein interactions prediction.
The following pages of this issue are four papers presenting current computational models for various interactions related to
proteins, representing only a small portion of current research. The following is a brief description of these papers.
In the opening paper of this issue, Xu et al. gave the process for prediction of posttranslational modification sites including
feature construction, algorithms, evaluation measurements and online web-servers. There are two types of posttranslational
modifications in proteins, and this paper summarized the methods and steps in the prediction of single and multiple PTM sites,
Hasan et al. discussed the latest developments and challenges in protein S-sulfenylation site prediction from available data
sets, algorithms and accessible services, and demonstrated the limitations and future prospects of computational prediction tools
One of the most important steps in developing functional genomics and proteomics prediction methods is to represent
biological sequences in fixed-length digital form, which can be further analyzed using machine learning algorithms. Several
software tools have been developed to apply these algorithms, and Zhao et al. reviewed the technical aspects of these software
Zhao et al. introduced a semi-supervised learning algorithm prediction model called random walk for lncRNA-protein
association prediction. This approach successfully avoided the difficulty of extracting negative data sets and features and
achieved better results than previous algorithms .
We would like to express our sincere gratitude to all authors and reviewers for their contribution to this issue. We would
also like to extend our appreciation to the Editor-in-Chief, Professor Ben M. Dunn and the editorial staff of Protein & Peptide
Letters for their excellent support and for providing us with the opportunity to pursue this hot topic issue.
In 1843, the nephew of Napoleon Bonaparte (i.e. Charles Lucien Bonaparte) established for the first time the proteinaceous
nature of snake venom, a complex substance secreted by glands to paralyze and kill either for predatory or defensive purposes.
Snake venoms represent a cocktail of thousands of diverse molecules, mainly proteins accounting for up to 95% of venom’s
dry weight. These proteins are mainly enzymes such as oxidoreductases e.g. catalase and oxidase; transferases such as ALT;
hydrolases including phospholipases, phosphodiesterases and hyaluronidases; lyases; (metalloproteinases) as well as peptides
(e.g. cardiotoxins, cytotoxin, hemotoxins alias hemorrhagins such as mucrotoxin or PLA2; postsynaptic neurotoxins, such as
cobratoxin or taipoxin). In addition to free amino acids, there are nucleosides, lipids, carbohydrates and metals coupled to
proteins, which account for the 5% of venom’s dry weight . The difference in chemical constituents of venoms among
various species is both topographical and onto-genic. Now-a-days, Omics technologies are contributing to a qualitative and
quantitative progress in the road map towards reconstruction of the natural history of venoms, which is of great interest in
diverse fields such as evolutionary ecology and biotechnology .
Snake venoms exert potent, selective and pleiotropic biological functions, which can lead to deleterious/toxic effects or
beneficial/exploitable solutions for biotechnological/medicinal applications .
It is worth noting that animal venoms have been used for a long time in folk medicine, mostly in Asian and Middle-East
countries and their applications are well documented as diuretic, cardiotonic, anesthetic or anti-cancers agents. For a bit more
than four decades, venoms and toxins of animals have been extensively explored for the management of human ailments like
hypertension, diabetes, long-lasting pains, cancers and HIV . Therefore, the complex chemical cocktail of venoms represents
a rich source of discovery and development of lead compounds.
An increasing number of in vitro and in vivo investigations have revealed the anti-carcinogenic properties of snake venoms
and purified toxins in various types of cancer (e.g. colorectal, cervical and breast cancers), produced mostly via the blocking of
progress of cancer, stopping of cell cycle, initiation of oxidative-stress mediated apoptosis, inhibition of pro-inflammatory
cytokines, and suppression of cancer metastasis. Thereby, anti-angiogenic effects by inhibiting Vascular Endothelial Growth
Factors (VEGF) were displayed by the Disintegrin Lebein isolated from snake venom [5-7]. Interestingly, those venoms or
purified venom toxins may be either an alternative or a complementary alternative to the currently available chemotherapeutic
The current and future challenges towards encapsulation of venoms or purified proteins in functionalized nanoparticles (e.g.
biocompatible and biodegradable liposomes/nanovesicles) are entailing in enhancing the anti-cancer potential while minimizing
the side effects (e.g. efficacy versus systemic or local toxicities) of free venom or free pure venom proteins . Various novel
nanoformulations are being tested, and their transfer from the benchmark to the bedside will certainly constitute a new hope for
more accurate theranostic strategies.
The crucial emphasis of our special thematic issue of Protein and Peptide Letters concerns the theranostic applications of
venom proteins isolated from different organisms (e.g. snakes, frogs, bees, spiders, scorpions, jellyfish, leeches, snails) to
diagnostic procedures like hemostasis testing and in therapeutics as anti-thrombotic agents in peripheral arterial thrombosis,
deep-vein thrombosis, myocardial infarction, stroke, HIV, diabetes, neurodegenerative disorders, hypertension and cancers.
We are thankful to all the Venomics researchers for their valuable contribution to this Special Issue. The stout efforts and
promise of the researchers always made the advancement of science to bring innovative perspectives and expectation for the
management of emerging chronic and complex disorders
The health threat caused by kidney diseases such as kidney cancer, chronic kidney disease and acute kidney failure, have a
high prevalence and represent a large burden of health care cost. Intensive research to develop novel strategies on various
aspects have been conducted in order to detect kidney function and treat kidney disease. One potential risk of Chronic Kidney
Disease (CKD) is end-stage renal disease, which requires costly renal replacement therapy such as dialysis and transplantation.
Kidney disease is conventionally assessed in terms of both overall renal function (glomerular filtration rate) and the presence of
kidney damage ascertained by either kidney biopsy or other markers of kidney damage such as proteinuria, abnormal urinary
sediment and abnormalities on imaging studies. Urinary proteome analysis has improved the current state of the art of CKD
detection and prediction. Additionally, in attempt to prevent or retard the progression of further kidney damage from CKD,
kidney specific drug targeting or renal drug delivery systems are used as an attractive strategy to reduce unwanted side effects
and to improve drug efficacy in the kidney tissue. Renal Cell Carcinoma (RCC) is the most prevailing kidney cancer. On one
hand, targeted therapies dramatically improved progression-free survival towards RCC patients compared with other traditional
chemotherapies and radiotherapies; on the other hand, immunotherapy has become an effective approach in the management of
RCC patient with metastatic disease because RCC has a high resistance of both chemotherapies and radiotherapies.
An increase in interesting preliminary results is being reported in aforementioned subtopics. As witnesses and practitioners
in this exciting area, however, we notice that the related communication in public domain is still limited due to the relatively
small number of scientists involved. Thus, we feel the necessity to compile a timely issue about the special topic “Protein and
Peptide Studies in Kidney Disease”, covering state-of-the-art research papers and expert reviews from this field. We are pleased
that Protein & Peptide Letters is willing to realize the idea with us.
The opening paper of this issue by Dr. Wu and co-author discusses several approaches to prolong the half-life of protein and
peptide drugs based on the unique structures of the glomerular capillary wall and mechanisms of glomerular filtration, such as
increasing the size and hydrodynamic diameter; increasing the negative charge to delay the filtration; and increasing plasma
protein binding to decrease plasma clearance . Next, Dr. Xu and coauthors describe current low molecular weight proteins
and peptide carriers for kidney targeted drug delivery systems, and outline the current status as well as give an outlook on the
further study .
The following two papers discuss the treatment of RCC. RCC, a type of kidney cancers, is one of the common malignant
tumors and accounts for approximately 4% of all cancers with high rates of morbidity and mortality. Dr. Yang and coauthors
discuss the role of therapeutic drug monitoring in the individual targeted treatment of RCC . The breakthroughs in the
understanding of tumor immune biology and the development of newer generation of cancer immunotherapies have provided a
new strategy for battling tumors. Recent progress of the use of immunotherapy with different agents for RCC are presented by
Dr. Gong and coauthors. In addition, the combination of different novel immunotherapeutic agents and other immune therapies
are also discussed .
The last review of this issue by Dr. Zeng and co-worker provide an overview of the varied probes from small molecular to
nanoparticle-based sensors that have been applied to the detection of various proteins from bench to bedside . The
quantitative measurement of protein and peptides will be benefit for the diagnosis and monitoring of kidney diseases in the
In summary, experts from different fields have showcased new results and expressed their opinions in this special thematic
issue of Protein & Peptide Letters. As the guest editor, I wish that this diverse collection of valuable intellectual contributions
will positively influence this emerging area and gain broad readership.
At the end, we would like to express our sincerest gratitude to all authors and referees for their invaluable contribution to
this issue. We would also like to extend our appreciation to Editor-in-Chief, Professor Ben M. Dunn and the staff of Protein &
Peptide Letters, especially Ms. Rukhshanda Rehman, for their excellent support and for providing us with the opportunity to
pursue this exciting project.
In developed countries, subfertility has become an increasing problem. Infertility is the inability to conceive after 12 months
of regular, unprotected intercourse. It is a worldwide problem, affecting 15% of couples that have unprotected intercourse. In
general, 50% of infertility cases are due to a solely female factor, pure male factor accounts for 20-30% of the problem, and the
remaining 20-30% is due to a combination of both male and female factors.
Again, one of the common complications of pregnancy is spontaneous pregnancy loss which occurs in an estimated 5-15%
of pregnancies. Although pregnancy loss has been associated to various hematologic, anatomic, hormonal, immune, and genetic
defects, in 30% of the cases, screening tests performed in cases of Repeated Pregnancy Loss (RPL) give negative results.
The last 10 to 15 years have witnessed rapid advances in approaches for the analyses of DNA sequence and structure. The
amount of information currently available about the genomes in human and animal reproduction has increased dramatically in
the past few years and the rate of its accumulation will continue to increase.
Also, proteomics has been widely used over recent years in almost all relevant biological samples (tissues, fluids, cells) to
depict both physiological and pathological states, and has yielded important results, including the significance of posttranslational
modifications in sperm and the intense immunological-inflammatory processes that take place during ovulation
and implantation. Proteomics represents a state-of-the-art, technology-driven science, which, in a high-throughput mode,
studies proteins and their post-translational modifications and interactions. This approach provides the opportunity to elucidate
complex biological processes and conditions, including fertilization, embryo implantation and differentiation and pregnancy.
Proteomics is providing useful insights into physiology of human reproduction and it is leading to the identification of
numerous proteins in biological tissues and fluids related to human reproduction that may be potential biomarkers and/or
treatment targets. In the area of reproduction, this approach seems to be the most promising and powerful platform that has
been recently applied in order to widely study the physiology and pathophysiology of reproduction and to identify novel
markers of diseases.
In the diagnostic of male infertility, semen analysis represents the cornerstone for the assessment of the male partner in subfertile
couples. Many studies, however, criticized the thresholds used to define male factor infertility using sperm concentration,
motility and morphology, the three classical sperm parameters measured by all laboratories. Additional markers of male fertility
have been proposed including the evaluation of anti-sperm antibodies, biochemical tests, kinematic parameters, sperm DNA
integrity and oxidative stress markers. However, due to the lack of a standardized and universally accepted assays and the
expensive or time-consuming techniques, these parameters did not reveal a role in the clinical workout of male infertility.
Therefore, several sources of clinical biomarkers have been proposed for female reproductive tract disease and cervical
mucus represents the most promising source of biomarkers reflecting the health of the male tract.
This special issue of Protein & Peptide Letters, entitled “Protein and peptide markers in reproduction” intends to showcase
new results and express the opinions of a selection of specialists who have expanded the field with their recent discoveries.
In the opening paper of this issue, Dr. Bibancos and co-authors discuss the potential use of proteomic platforms in the
workflow of couple infertility in clinical practice. Beyond the identification of the oocytes and embryos with the best
developmental potentials in assisted reproductive techniques or prediction of a pregnancy’s outcome, it may add significant
information for the diagnosis of both male and female infertility .
The most abundant sperm nuclear proteins are protamins. Dr. Oliva, in addition to briefly reviewing the studies available so
far about protamine alterations and male infertility, provided a very comprehensive protocol for the successful implementation
of protamine extraction and analysis into the laboratory routine, including protocol variations for specific procedure
The post-genomic approaches in the study of male sperm function, consisting of different methodologies for concurrently
testicular transcriptome studies, protein compositional analysis and metabolomics findings, have been reviewed by Dr. Dipresa
Dr. Luca summarized some of the recent findings regarding the immunomodulatory role of Sertoli cells, and especially the
key Sertoli cell regulatory proteins that are associated with the well-defined immune privileged status of the testis .
Dr. De Toni analyzed the most recent cues about the molecular bases of the known process of sperm thermotaxis, and the
possible pathophysiological and therapeutic repercussions deriving from the characterization of sperm proteins acting as
Furthermore, the expression in sperm surface of specific nicotine receptors might represent a marker of sperm smokingrelated
damage. Dr. La Vignera discussed in his manuscript the mechanism by which nicotine alters spermatozoa and the
expression pattern of nicotinic receptors subunits in human spermatozoa .
In addition Dr. Di Nicuolo reviewed the role of inflammosome in female reproduction and namely in RPL .
Dr. Fernandez-Hermida in her review article collected relevant knowledge about the physicochemical properties and
functions of the cervical mucus, including its important role as a clinical marker of female fertility, and draws attention to
cervical mucus as the best source of potential protein biomarkers to assess the health of female genital tract .
Proteomic platforms have been applied to identify novel markers of disease in seminal plasma. Dr. Grande reported a
research article aimed to identify, for the first time, novel seminal biomarkers for the male tract infection by Enterococcus
faecalis, using proteomic profiling, in order to understand the effect of E. faecalis on the physiopathology of male reproduction
Among the proposed markers of Male Accessory Gland Inflammation (MAGI), soluble urokinase-type plasminogen
activator receptor (suPAR) has been recently proposed as a reliable and sensitive marker. In the study by Milardi et al., the role
of suPAR as a protein marker of MAGI was confirmed in hypogonadism, supporting the hypothesis that hypogonadism induces
a state of inflammation in male accessory glands which is involved in male infertility .
In summary, experts from the field of male and female reproduction have presented new results and reviewed the current
advances in their specific area in this special thematic issue of Protein & Peptide Letters. As the guest editors, we wish that this
diverse collection of articles will gain broad readership.
The protein and peptide analysis provides a good starting point to discover new reproduction-related proteins; however,
further functional analyses should be conducted to gain a specific role for fertility traits in human reproduction metabolism. The
comprehensive proteomic profiling of human reproduction and its pathology constitutes a major challenge for the international
We would like to express our sincere gratitude to all authors and referees for their contribution to this issue. We would also
like to extend our appreciation to the Editor-in-Chief, Professor Ben M. Dunn and the editorial staff of Protein & Peptide
Letters, especially Ms Amna Sajid, for their excellent support and for providing us with the opportunity to pursue this hot topic
Global warming, diminishing fossil fuel resources and growing energy requirements have kindled the
research on alternative fuels. Moreover, cleaner production and sustainable consumption of industrial
products have become forefront research areas in recent years. The special issue “Recent trends in
biofuels and bio-industry” focusses on the emerging trends in this area. Original research articles
presenting the cornerstone technologies to address the bottleneck issues in biofuel and bio-industrial
processes, and critical review articles analyzing the challenges and discussing the future opportunities are
welcomed. The submissions focusing on the characterization/engineering of novel proteins/enzymes of
industrial/biofuel importance, identification/engineering/synthesis of metabolic pathways for biofuels and
industrial chemicals, would be highly appreciated.
In the last decade, materials synthesis and processing under conditions with low energy consumptions have been gathering attractive interests for building sustainable societies. Because biominerals are precisely-designed composite materials made from the combinations of inorganic minerals such as calcium carbonate, silica, hydroxyapatite and organic template molecules such as proteins and peptides under ambient conditions, biomimetic production of organic-inorganic hybrid nanomaterials would be one of the approaches to provide a variety of morphologies and arrangements of inorganic components for fabrications and applications. So far, many scientists/chemists have devoted their great efforts to control morphologies of inorganic precipitates using organic compounds such as polymers, surfactants, and so on. Proteins and peptides are promising organic template molecules for use in the biomimetic process because they confer several advantages: 1) proteins and peptides can offer milder conditions for the production, 2) proteins and peptides can impose on the size, shape, and crystal structure of the inorganic products, 3) proteins and peptides can offer the potential to produce materials with highly specific or multiple functions. Therefore, the rapid progress in the development of synthesis and processing of organic-inorganic hybrid materials is evident and the compilation of the subtopics listed below would appear to be timely. This theme issue intends to offer for understanding new knowledge on protein- and/or peptide-associated materials and propose unprecedented and fundamental concepts as well as some directions to their practical applications. The theme issue included in the following potential subtopics, but are not limited to:
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