Current Protein and Peptide Science - Volume 20, Issue 12, 2019

Sexually Transmitted Diseases (STDs) refer to a variety of clinical syndromes and infections caused by pathogens that can be acquired and transmitted through sexual activity. Among STDs widely reported in the literature, viral sexual diseases have been increasing in a number of cases globally. This emphasizes the need for prevention and treatment. Among the methods widely used in drug planning are Computer-Aided Drug Design (CADD) studies and molecular docking which have the objective of investigating molecular interactions between two molecules to better understand the three -dimensional structural characteristics of the compounds. This review will discuss molecular docking studies applied to viral STDs, such as Ebola virus, Herpes virus and HIV, and reveal promising new drug candidates with high levels of specificity to their respective targets.

Prediction of physicochemical and biochemical behavior of peptides is an important and attractive task of the modern natural sciences, since these substances have a key role in life processes. The Monte Carlo technique is a possible way to solve the above task. The Monte Carlo method is a tool with different applications relative to the study of peptides: (i) analysis of the 3D configurations (conformers); (ii) establishment of quantitative structure – property / activity relationships (QSPRs/QSARs); and (iii) development of databases on the biopolymers. Current ideas related to application of the Monte Carlo technique for studying peptides and biopolymers have been discussed in this review.

The field of enzyme inhibition is a tremendous and quickly growing territory of research. Urease a nickel containing metalloenzyme found in bacteria, algae, fungi, and plants brings hydrolysis of urea and plays important role in environmental nitrogen cycle. Apart from this it was found to be responsible for many pathological conditions due to its presence in many microorganisms such as H. Pylori, a ureolytic bacteria having urease which elevates pH of gastric medium by hydrolyzing urea present in alimentary canal and help the bacteria to colonize and spread infection. Due to the infections caused by the various bacterial ureases such as Bacillus pasteurii, Brucella abortus, H. pylori, H. mustelae, Klebsiella aerogenes, Klebsiella tuberculosis, Mycobacterium tuberculosis, Pseudomonas putida, Sporosarcina pasteurii and Yersinia enterocolitica, it has been the current topic of today’s research. About a wide range of compounds from the exhaustive literature survey has been discussed in this review which is enveloped into two expansive classes, as Inhibitors from synthetic origin and Inhibitors from natural origin. Moreover active site details of enzyme, mechanism of catalysis of substrate by enzyme, uses of plant urease and its pathogenic behavior has been included in the current review. So, overall, this review article diagrams the current landscape of the developments in the improvements in the thriving field of urease inhibitory movement in medicinal chemistry from year 2010 to 2018, with an emphasis on mechanism of action of inhibitors that may be used for more development of recent and strong urease inhibitors and open up new doors for assist examinations in a standout amongst the most lively and promising regions of research.

Antimicrobial Resistance (AMR) represents a serious threat to health and the global economy. However, interest in antibacterial drug development has decreased substantially in recent decades. Meanwhile, anti-virulence drug development has emerged as an attractive alternative to fight AMR. Although several macromolecular targets have been explored for this goal, their druggability is a vital piece of information that has been overlooked. This review explores this subject by showing how structure- based freely available in silico tools, such as PockDrug and FTMap, might be useful for designing novel inhibitors of the pyocyanin biosynthesis pathway and improving the potency/selectivity of compounds that target the Pseudomonas aeruginosa quorum sensing mechanism. The information provided by hotspot analysis, along with binding site features, reveals novel druggable targets (PhzA and PhzS) that remain largely unexplored. However, it also highlights that in silico druggability prediction tools have several limitations that might be overcome in the near future. Meanwhile, anti-virulence drug targets should be assessed by complementary methods, such as the combined use of FTMap/PockDrug, once the consensus druggability classification reduces the risk of wasting resources on undruggable proteins.

Legume proteins are precursors of bioactive components, such as peptides. In the present paper, different types of legume as sources of bioactive peptides and hydrolysates are considered and discussed based on their anti-inflammatory effect. Peptides with anti-inflammatory activity were included from in vitro and in vivo studies. Current strategies for obtaining bioactive peptides, as well as their structure and impact on health, were also reviewed. It was discovered that peptides derived from legume protein, mainly soybean and bean, can regulate several inflammatory markers, which include prostaglandin E2 (PGE2), nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX- 2), cytokines, and chemokines. So far, lunasin, VPY and γ-glutamyl peptides have been identified with anti-inflammatory activity but their mechanisms have not been fully elucidated. Furthermore, it is necessary to gather more information about hydrolysates containing peptides and single peptides with antiinflammatory activity. Considering the wide diversity, legume may be promising components to produce peptides efficient to ameliorate inflammatory disorders.

Out of multiple therapeutic targets, DPP-IV is the lead target for the treatment of type 2 diabetes. Natural products have always been available for the possible lead generation against various diseases and disorders. In the present review, we have covered various natural sources which have experimentally validated anti-diabetic activity for type 2 diabetic patients with specific focus on the DPP-IV inhibition. Out of all, the most potent DPP-IV inhibitors were found to be resveratrol, luteolin, apigenin and flavone having activity in nanomolar range. Standard drugs like sitagliptin, saxagliptin, and diprotin A have complex structures as compared to these phenolic compounds. Flavonoids and phenolic compounds have their added advantages in being present in a number of functional foods and carry antioxidant properties as well. So, the scientists working on the new chemical entity hunting for the type 2 diabetes treatment can also explore these natural sources for lead generation.

Protein folding is the process by which a polypeptide chain acquires its functional, native 3D structure. Protein misfolding, on the other hand, is a process in which protein fails to fold into its native functional conformation. This misfolding of proteins may lead to precipitation of a number of serious diseases such as Cystic Fibrosis (CF), Alzheimer’s Disease (AD), Parkinson’s Disease (PD), and Amyotrophic Lateral Sclerosis (ALS) etc. Protein Quality-control (PQC) systems, consisting of molecular chaperones, proteases and regulatory factors, help in protein folding and prevent its aggregation. At the same time, PQC systems also do sorting and removal of improperly folded polypeptides. Among the major types of PQC systems involved in protein homeostasis are cytosolic, Endoplasmic Reticulum (ER) and mitochondrial ones. The cytosol PQC system includes a large number of component chaperones, such as Nascent-polypeptide-associated Complex (NAC), Hsp40, Hsp70, prefoldin and T Complex Protein-1 (TCP-1) Ring Complex (TRiC). Protein misfolding diseases caused due to defective cytosolic PQC system include diseases involving keratin/collagen proteins, cardiomyopathies, phenylketonuria, PD and ALS. The components of PQC system of Endoplasmic Reticulum (ER) include Binding immunoglobulin Protein (BiP), Calnexin (CNX), Calreticulin (CRT), Glucose-regulated Protein GRP94, the thiol-disulphide oxidoreductases, Protein Disulphide Isomerase (PDI) and ERp57. ER-linked misfolding diseases include CF and Familial Neurohypophyseal Diabetes Insipidus (FNDI). The components of mitochondrial PQC system include mitochondrial chaperones such as the Hsp70, the Hsp60/Hsp10 and a set of proteases having AAA+ domains similar to the proteasome that are situated in the matrix or the inner membrane. Protein misfolding diseases caused due to defective mitochondrial PQC system include medium-chain acyl-CoA dehydrogenase (MCAD)/Short-chain Acyl-CoA Dehydrogenase (SCAD) deficiency diseases, hereditary spastic paraplegia. Among therapeutic approaches towards the treatment of various protein misfolding diseases, chaperones have been suggested as potential therapeutic molecules for target based treatment. Chaperones have been advantageous because of their efficient entry and distribution inside the cells, including specific cellular compartments, in therapeutic concentrations. Based on the chemical nature of the chaperones used for therapeutic purposes, molecular, chemical and pharmacological classes of chaperones have been discussed.