Vol 25, No 6 (2024)

Life Sciences

Molecular Players at the Sorting Stations of Malaria Parasite ‘Plasmodium falciparum’

Kaur J., Mishra P., Hora R.

Abstract

The apicomplexan pathogenic parasite ‘Plasmodium falciparum’ (Pf) is responsible for most of the malaria related mortality. It resides in and refurbishes the infected red blood cells (iRBCs) for its own survival and to suffice its metabolic needs. Remodeling of host erythrocytes involves alteration of physical and biochemical properties of the membrane and genesis of new parasite induced structures within the iRBCs. The generated structures include knobs and solute ion channels on the erythrocyte surface and specialized organelles i.e. Maurer’s clefts (MCs) in the iRBC cytosol. The above processes are mediated by exporting a large repertoire of proteins to the host cell, most of which are transported via MCs, the sorting stations in parasitized erythrocytes. Information about MC biogenesis and the molecules involved in maintaining MC architecture remains incompletely elucidated. Here, we have compiled a list of experimentally known MC resident proteins, several of which have roles in maintaining its architecture and function. Our short review covers available data on the domain organization, orthologues, topology and specific roles of these proteins. We highlight the current knowledge gaps in our understanding of MCs as crucial organelles involved in parasite biology and disease pathogenesis.

Current Protein & Peptide Science. 2024;25(6):427-437
pages 427-437 views

The Disulfide Bond-Mediated Cyclization of Oral Peptides

Yao C., Ye G., Yang Q., Chen Z., Yang M.

Abstract

‘Structure determines function’ is a consensus in the current biological community, but the structural characteristics corresponding to a certain function have always been a hot field of scientific exploration. A peptide is a bio-active molecule that is between the size of an antibody and a small molecule. Still, the gastrointestinal barrier and the physicochemical properties of peptides have always limited the oral administration of peptides. Therefore, we analyze the main ways oral peptide conversion strategies of peptide modification and permeation enhancers. Based on our analysis of the structure of natural oral peptides, which can be absorbed through the gastrointestinal tract, we believe that the design strategy of natural stapled peptides based on disulfide bonds is good for oral peptide design. This cannot only be used to identify anti-gastrointestinal digestive structural proteins in nature but also provide a solid structural foundation for the construction of new oral peptide drugs.

Current Protein & Peptide Science. 2024;25(6):438-442
pages 438-442 views

A Review of the Leishmanicidal Properties of Lectins

Grangeiro Y., Santos A., Barbosa F., Roma R., Souza R., Silva C., Teixeira C.

Abstract

Lectins are proteins widely distributed among plants, animals and microorganisms that have the ability to recognize and interact with specific carbohydrates. They have varied biological activities, such as the inhibition of the progression of infections caused by fungi, bacteria, viruses and protozoa, which is related to the interaction of these proteins with the carbohydrates present in the cell walls of these microorganisms. Leishmaniasis are a group of endemic infectious diseases caused by protozoa of the genus Leishmania. In vitro and in vivo tests with promastigotes and amastigotes of Leishmania demonstrated that lectins have the ability to interact with glycoconjugates present on the cell surface of the parasite, it prevents their development through various mechanisms of action, such as the production of ROS and alteration of membrane integrity, and can also interact with defense cells present in the human body, thus showing that these molecules can be considered alternative pharmacological targets for the treatment of leishmaniasis. The objective of the present work is to carry out a bibliographic review on lectins with leishmanicidal activity, emphasizing the advances and perspectives of research in this theme. Through the analysis of the selected studies, we were able to conclude that lectins have great potential for inhibiting the development of leishmaniasis. However, there are still few studies on this subject.

Current Protein & Peptide Science. 2024;25(6):443-453
pages 443-453 views

Combating Aminoglycoside Resistance: From Structural and Functional Characterisation to Therapeutic Challenges with RKAAT

Otun S., Graca R., Achilonu I.

Abstract

A comprehensive knowledge of aminoglycoside-modifying enzymes (AMEs) and their role in bacterial resistance mechanisms is urgently required due to the rising incidence of antibiotic resistance, particularly in Klebsiella pneumoniae infections. This study explores the essential features of AMEs, including their structural and functional properties, the processes by which they contribute to antibiotic resistance, and the therapeutic importance of aminoglycosides. The study primarily examines the Recombinant Klebsiella pneumoniae Aminoglycoside Adenylyl Transferase (RKAAT), particularly emphasizing its biophysical characteristics and the sorts of resistance it imparts. Furthermore, this study examines the challenges presented by RKAAT-mediated resistance, an evaluation of treatment methods and constraints, and options for controlling infection. The analysis provides a prospective outlook on strategies to address and reduce antibiotic resistance. This extensive investigation seeks to provide vital insights into the continu

Current Protein & Peptide Science. 2024;25(6):454-468
pages 454-468 views

CTXP, The Major Cobra Toxin Peptide from Naja Naja Oxiana Venom; A Promising Target for Antivenom Agent Development

Chafi M., Eslamnezhad-Namin M., Dastjerdeh M., Zareinejad M., Oghalaie A., Bagheri K., Kazemi-Lomedasht F., Karimi G., Razzaghi-Abyaneh M., Seyedjavadi S., Behdani M.

Abstract

Background and Objective:Snakebite envenoming is a serious public health issue causing more than 135,000 annual deaths worldwide. Naja naja oxiana is one of the most clinically important venomous snakes in Iran and Central Asia. Conventional animal-derived polyclonal antibodies are the major treatment of snakebite envenoming. Characterization of venom components helps to pinpoint the toxic protein responsible for clinical manifestations in victims, which aids us in developing efficient antivenoms with minimal side effects. Therefore, the present study aimed to identify the major lethal protein of Naja naja oxiana by top-down proteomics.

Methods:Venom proteomic profiling was performed using gel filtration (GF), reversed-phase (RP) chromatography, and intact mass spectrometry. The toxicity of GF-, and RP-eluted fractions was analyzed in BALB/c mice. The rabbit polyclonal antisera were produced against crude venom, GF fraction V (FV), and RP peak 1 (CTXP) and applied in neutralization assays.

Results:Toxicity studies in BALB/c identified FV as the major toxic fraction of venom. Subsequently, RP separation of FV resulted in eight peaks, of which peak 1, referred to as "CTXP" (cobra toxin peptide), was identified as the major lethal protein. In vivo neutralization assays using rabbit antisera showed that polyclonal antibodies raised against FV and CTXP are capable of neutralizing at least 2-LD50s of crude venom, FV, and CTXP in all tested mice.

Conclusion:Surprisingly, the Anti-CTXP antibody could neutralize 8-LD50 of the CTXP peptide. These results identified CTXP (a 7 kDa peptide) as a potential target for the development of novel efficient antivenom agents.

Current Protein & Peptide Science. 2024;25(6):469-479
pages 469-479 views

Heparin Oligosaccharides as Vasoactive Intestinal Peptide Inhibitors via their Binding Process Characterization

Li M., Xue Y., Chi L., Jin L.

Abstract

Background:It has been proven that vasoactive intestinal peptide (VIP) was involved in the pathogenesis of prostate cancer. Cardin et al. found that by an alanine scan, the heparin-binding site on VIP was exactly the same sequence in VIP and its receptor. Therefore, heparin could competitively block the binding of VIP and its receptor. However, the structure-activity relationship between heparin and VIP has not been reported, especially in terms of the sequence and sulfation patterns of heparin oligosaccharides upon binding to VIP.

Objective:The binding process between heparin oligosaccharides and VIPA variety of experiments was designed to study the structure-activity relationship between heparin oligosaccharides and VIP.

Methods:Heparin was enzymatically digested and purified to produce heparin oligosaccharides, and the structures were characterized by NMR. The binding capacity between heparin oligosaccharides and VIP was analyzed by GMSA and ITC experiments. The binding between heparin oligosaccharides and VIP was simulated using a molecular docking program to show the complex. ELISA assay was used to investigate the effect of non-anticoagulant heparin oligosaccharides on the VIP-mediated cAMP/PKA signaling pathway in vitro.

Results:The results indicated that both the length and the sulfation pattern of heparin oligosaccharides affected its binding to VIP. VIP could induce the expression of cAMP at a higher level in PC3 cells, which could be regulated by the interaction of heparin oligosaccharides and VIP.

Conclusion:The binding between heparin oligosaccharides and VIP could block the binding between VIP and its receptor on tumor cells. Downloading the regulation of the expression level of cAMP could possibly further affect the subsequent activation of PKA. These non-anticoagulant heparin oligosaccharides may block the VIP-mediated cAMP/PKA signaling pathway and thus exert their antitumor activity.

Current Protein & Peptide Science. 2024;25(6):480-491
pages 480-491 views

Spectroscopic Analysis of the Effect of Ibuprofen Degradation Products on the Interaction between Ibuprofen and Human Serum Albumin

Ploch-Jankowska A.

Abstract

Background:Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are one of the most commonly used groups of medicinal compounds in the world. The wide access to NSAIDs and the various ways of storing them due to their easy accessibility often entail the problem with the stability and durability resulting from the exposure of drugs to external factors. The aim of the research was to evaluate in vitro the mechanism of competition between ibuprofen (IBU) and its degradation products, i.e., 4'-isobutylacetophenone (IBAP) and (2RS)-2-(4- formylphenyl)propionic acid (FPPA) during transport in a complex with fatted (HSA) and defatted (dHSA) human serum albumin.

Methods:The research was carried out using spectroscopic techniques, such as spectrophotometry, infrared spectroscopy and nuclear magnetic resonance spectroscopy

Results:The comprehensive application of spectroscopic techniques allowed, among others, for the determination of the binding constant, the number of classes of binding sites and the cooperativeness constant of the analyzed systems IBU-(d)HSA, IBU-(d)HSA-FPPA, IBU-(d)HSA-IBAP; the determination of the effect of ibuprofen and its degradation products on the secondary structure of albumin; identification and assessment of interactions between ligand and albumin; assessment of the impact of the presence of fatty acids in the structure of albumin and the measurement temperature on the binding of IBU, IBAP and FPPA to (d)HSA.

Conclusion:The conducted research allowed us to conclude that the presence of ibuprofen degradation products and the increase in their concentration significantly affect the formation of the IBU-albumin complex and thus, the value of the association constant of the drug, changing the concentration of its free fraction in the blood plasma. It was also found that the presence of an ibuprofen degradation product in a complex with albumin affects its secondary structure.

Current Protein & Peptide Science. 2024;25(6):492-506
pages 492-506 views