Current Protein and Peptide Science - Volume 19, Issue 10, 2018

In the last few decades, advances in the cancer chemotherapy have been a marked success. A large number of anticancer drugs currently in use include drugs based on platinum complexes such as cisplatin, base analogues such as 5-florouracil and some ruthenium drugs. This review provides a bird's eye view of interaction of a number of clinically important drugs currently in use that show covalent or non-covalent interaction with serum proteins. Platinum drug-cisplatin interacts covalently and alters the function of the key plasma protease inhibitor molecule -alpha-2-macroglobulin and induces the conformational changes in the protein molecule and inactivates it. 5-fluorouracil (5-FU) is extensively metabolized and at physiological concentrations, is found to be associated with Human Serum Albumin (HSA). Similarly ruthenium compounds bind tightly to plasma proteins- serum albumin and serum transferrin, modifying their biological activity and increasing the toxicity of drug to cancer cells. Insight into varied anticancer drug- protein interaction will go a long way in understanding in totality of the mechanism of action of any anticancer drug and its possible effects/side effects.

Protein-protein interaction (PPI) is necessary for most of the biological processes and requisite for host-pathogen communication. Most of the threatening human diseases are caused by different types of interactions of proteins with their prior infected proteins or with pathogen's proteins. Understanding of involved mechanisms of interacting pairs, functional domains and characterizing specific molecular interaction of host and pathogen is critical. In this era of advanced research in medical and pharmaceutical sciences, the treatment of severe diseases is being tackled at genetic and PPI level. In this review, a brief introduction and application of PPI is described. Moreover, the classifications of PPI and their application in diseases are highlighted. Furthermore, methods for prediction of PPI are also discussed including brief introduction and update on detection techniques. We hope this review will prove to be very helpful for researchers to get better understanding and update on PPI.

Currently it is well known that all biological drugs, including those with a fully human structure, are capable of inducing a host immune response known as immunogenicity [1]. The presence of ADAs can condition the drug´s level and action, thus modifying the therapeutic effect and even the safety profile by its mechanism of action - neutralizing or non-neutralizing - and / or an increase in its clearance. Immunogenicity is a dynamic factor to be taken into account in biological therapy, especially in long-term treatments, and as a relevant aspect in the assessment of secondary response loss [2]. With the above, not only the knowledge but also the management of the immunogenicity of the different biological treatments, represent a useful instrument for optimization of the strategies of use for each drug, and in the design of predictive models of response, which finally permits a significant improvement in the efficacy and safety profile, aiming to a personalization of the therapies, especially in patients with autoimmune diseases, genetic disorders and cancer [3]. This review summarizes the events of immunogenicity that produce the biological drug, the factor that influence to immunogenicity and the assessment of immunogenicity.

Proteins have played a very important role in the drug industry for developing treatments of various diseases such as auto-immune diseases, cancer, diabetes, mental disorder, metabolic disease, and others. Therapeutic proteins have high activity and specificity but they have some limitations such as short half-life, poor stability, low solubility and immunogenicity, so they cannot prolong their therapeutic activity. These shortcomings have been rectified by using polymers for the conjugation with proteins. The conjugates of protein-polymer improves the half-lives, stability and makes them non-immunogenic. Poly(ethylene glycol) (PEG), is widely used in the delivery of proteins because it is the current gold standard for stealth polymers in the emerging field of polymer-based delivery as compared to various biodegradable polymers. PEGylation enhances the retention of therapeutic proteins, effectively alters the pharmacokinetics and enhances the pharmaceutical value. Smart polymer have been used to cope with the pathophysiological environment of target site and have imposed less toxic effects.The contents of this article are challenges in formulation of therapeutic proteins, synthetic routes of conjugates, smart polymer–protein conjugates and also some advantages/disadvantages of polymers as a carrier system of proteins.

Milk fat globule membrane (MFGM) is one of the milk components that is produced by the lactating mammary glands and released to the milk in the form of vesicles. MFGM surrounds milk fat globule secreted by the milk producing cells and has a complex structure containing various lipids (e.g., triacylglycerides, phospholipids, and cholesterol), proteins and other macromolecules. Among the proteinaceous components of MFGM is lactadherin, also known as milk fat globule-EGF factor 8 protein (MFG-E8). Being one of the main proteins present in MFGM, lactadherin is related to milk secretion, has antimicrobial and antiviral effects, and plays important roles in the immune defense as one of the immune system molecules. Furthermore, lactadherin belongs to the family of secreted extracellular matrix proteins, and clearly can be considered as a multifunctional (or moonlighting) glycoprotein involved in regulation of many biological and physiological processes, such as angiogenesis, atherosclerosis, haemostasis, phagocytosis, and tissue remodeling. This review focuses on the similarities and differences of lactadherin among different species and describes the main functions of this protein, as well as its structure.

Dengue fever has become an imminent threat to international public health because of global warming and climate change. The World Health Organization proclaimed that more than 50% of the world's population is at risk of dengue virus (DENV) infection. Therefore, developing a clinically approved vaccine and effective therapeutic remedy for treating dengue fever is imperative. Peptide drug development has become a novel pharmaceutical research field. This article reviews various peptidesbased antimicrobial agents targeting three pathways involved in the DENV lifecycle. Specifically, they are peptide vaccines from immunomodulation, peptide drugs that inhibit virus entry, and peptide drugs that interfere with viral replication. Many antiviral peptide studies against DENV have been conducted in animal model trials, and progression to clinical trials for these promising peptide drugs is anticipated.

The relation between dietary fibre and the well-being of human and other monogastrics has recently became a hot topic as shown by the increasing number of publications of the related research. The aim of this review is to describe - through a logical approach - the scientific suggestion linking possible benefits of dietary fibre on nutritional components and their effect on the gastrointestinal composition in relation to disease conditions in humans and animals. Dietary fibre plays a key role in: influencing blood glucose or insulin concentrations, stool bulkiness, reducing the pH within the digestive tract, synthesising volatile fatty acids (VFA), reducing intestinal transit time, stimulating growth of intestinal microbes, and constructively enhancing various blood parameters. The available literature suggests that fibre influences the bioavailability of nutrients and maintains the host's well-being by controlling disorders and disease prevalent with a Western way of living such as constipation and diarrhoea, diabetes, obesity, gastrointestinal inflammation, atherosclerosis, and colon cancer. Although there are some studies demonstrating that dietary fibre may be effective in the prevention and treatment of these disorders, the mechanisms involved are yet to be understood.

Arranging into well-organized fibrillar aggregate, commonly known as amyloid fibril is an inherent property of any polypeptide chain. Amyloid fibrils are associated with a number of severe human pathologies like the Alzheimer's disease, Parkinson's disease, type2 diabetes and many more. Recent studies suggest that most of the fibrils are inert and extremely stable, thus could be used for the bionanotechnological applications. As the native state is protected by evolution from aggregation under physiological condition, understanding the structure of aggregation precursor state (APS) will be of extreme importance to decode mechanism of its formation and prevention. This review article includes the recent studies of identification and characterization of possible conformations of proteins which can act as APS. The literature regarding the research in this field revealed that any conformation ranging from native-like state to completely unfolded state could be an APS. The structural characteristics of the APS depend on the protein and on its surrounding environment. From this review of literatures, we conclude that exposure of aggregation-prone segments is the requirement for amyloid fibril formation and the amyloid state seems to be the most stable known physical state of the proteins. This means all conformations of proteins with exposed aggregation-prone segments can promote intermolecular interactions and channel to amyloid fibril pathway to acquire their minimum energy state.