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Current Protein and Peptide Science - Volume 26, Issue 8, 2025

Volume 26, Issue 8

Volume 26, Issue 8, 2025

    • Inhibitors of Type II NADH Dehydrogenase Enzyme: A Review

      https://doi.org/10.2174/0113892037350396250213115109

      Mitochondria are organelles in eukaryotic organisms with an electron transport chain consisting of four complexes ( CI, CII, CIII, and CIV) on the inner membrane, which have functions such as providing energy, electron transport, and generating proton gradients. NADH dehydrogenase type 2 (NDH-2), widely found in bacterial, plant, fungal and protist mitochondria, is a nonproton-pumping single-subunit enzyme bound to the surface of the inner mitochondrial membrane that partially replaces NDH-1. NDH-2 has a crucial role in the energy metabolism of pathogenic microorganisms, and the lack of NDH-2 or its homologs in humans makes NDH-2 an essential target for the development of antimicrobial drugs. There is a wide variety of pathogenic microorganisms that invade the human body and cause diseases; therefore, more and more inhibitors targeting NDH-2 of different pathogenic microorganisms continue to be reported. This paper first reviews the structure and function of NDH-2 and summarizes the classification of compounds targeting NDH-2. Given the relative paucity of inhibition mechanisms for NDH-2, which has greatly hindered the development of targeted drugs, the article concludes with a summary of two possible mechanisms in action: allosteric inhibition and competitive inhibition. This review will provide theoretical support for the subsequent molecular design and modification of drugs targeting the pathogenic microorganism NDH-2.

    • A Valuable Target for Therapy: The Metalloproteinase ADAM10

      https://doi.org/10.2174/0113892037348066250117070824

      A special kind of posttranslational process known as proteolytic cleavage controls the half-lives and functions of several extracellular and intracellular proteins. The metalloproteinase ADAM10 has attracted attention because it cleaves a growing amount of protein substrates close to the extracellular membrane leaflet. The process known as “ectodomain shedding” controls the turnover of certain transmembrane proteins that are essential for receptor signaling and cell adhesion. It may trigger nuclear transport, intramembrane proteolysis, and cytoplasmic domain signaling. Additional human illnesses linked to ADAM10 include cancer, immune system malfunction, and neurodegeneration. The difficulty in targeting proteases for medicinal reasons stems from the many substrates that these enzymes, particularly ADAM10, have. It is usually necessary to precisely identify the therapeutic beneficial window of use since blocking or accelerating a particular protease activity is linked with undesirable side effects. More knowledge of the regulatory pathways governing ADAM10 expression, subcellular localization, and activity will probably lead to the identification of viable therapeutic targets, enabling more targeted and precise manipulation of the enzyme's proteolytic activity.

    • Exploring Placental Protein-Target Protein Interactions: and Approaches for Osteoarthritis Therapy

      https://doi.org/10.2174/0113892037366889250322043039
      Background

      Osteoarthritis (OA) is a persistent joint condition marked by gradual softening and breakdown of articular cartilage. Current research in OA treatment explores biologics that target proinflammatory cytokines and proteases, as well as promote chondrocyte regeneration and cartilage repair. Human placental tissues, abundant in anti-catabolic factors, can mitigate cartilage degradation by inhibiting protease expression and maintaining cartilage homeostasis in the presence of anabolic factors.

      Objective

      This investigation examined placental protein interactions with proteases and OA target proteins through protein-protein docking and dynamic studies.

      Methods

      The NCBI conserved domain database was utilized to predict functional protein domains. Protein sequence motifs were identified using literature, the MEME suite tool, and the MyHits database. The Expasy-ProtParam online tool was employed to analyze protein physical parameters. ClusPro Advanced Options was used to dock binding site residues of selected placental proteins against specific OA target proteins, while PDBsum and Biovia Discovery Studio were used to visualize and examine molecular interactions. A 100 ns molecular dynamics (MD) study was conducted using DESMOND software.

      Results

      Protein-protein docking revealed strong interactions of placental proteins with docking scores ranging from -1700 to -2450.3 against proteases and -900 to -1400 against specific target proteins. PDBsum analysis of placental protein-target protein docked complexes revealed residue interactions, hydrogen bonds, and non-bonded contacts. Molecular dynamics simulations further confirmed the stability of these complexes, indicating favorable protein-protein interactions (PPIs). The anti-inflammatory activity of human placental tissue against lipopolysaccharide-induced macrophages was investigated using flow cytometry.

      Conclusion

      These results provide a foundation for future experimental studies to confirm the predicted interactions and to explore their potential therapeutic applications in OA treatment. Additionally, patients with OA and other arthritic conditions could benefit from the biologics chondroprotective biofactors, which serve as a promising alternative to conventional knee replacement surgery.

    • Synthesis of Silver Nanoparticle within Self-Assembling Ultrashort Peptide Hydrogel as Antibacterial with Wound Healing Properties

      https://doi.org/10.2174/0113892037367553250327084808
      Introduction/Objectives

      Silver nanoparticles (AgNPs) are promising antimicrobial agents, but their synthesis often involves toxic reducing agents. To address this, we developed a green synthesis methodology employing an approach for synthesizing AgNPs within self-assembled ultrashort peptide hydrogels through photochemical synthesis, eliminating the need for toxic chemicals.

      Methods

      A novel tetrapeptide was designed and synthesized to form hydrogels in aqueous solutions. AgNPs were incorporated into the hydrogel photochemical synthesis using sunlight. The hydrogel and AgNPs were characterized through spectroscopic and microscopic techniques. The antibacterial efficacy of the AgNP-loaded hydrogel was assessed against gram-positive and gram-negative bacteria, and its wound-healing potential in mammalian cell lines was evaluated.

      Results

      Among the peptides synthesized, PHG-2 formed a hydrogel at a 1% w/v concentration in aqueous solution. Characterization using the gel inversion assay, circular dichroism (CD) spectroscopy, and transmission electron microscopy (TEM) revealed uniform nanofibril self-assembly. UV spectroscopy and TEM confirmed the formation of AgNPs within the hydrogel. While the peptide hydrogel exhibited moderate antibacterial activity alone, the AgNP-loaded hydrogel demonstrated synergistic antibacterial effects against methicillin-resistant (MRSA) and . A docking study of all the synthesized peptides was performed against FmtA (an enzyme for cell wall synthesis of MRSA) and results were correlated with the obtained docking score. The silver-loaded peptide hydrogel showed a twofold increase in antibacterial activity against MRSA compared to silver nitrate solutions. The hydrogel significantly promoted wound healing in HEK-293T and MCF-7 cells compared to the control.

      Conclusion

      This study introduces a novel ultrashort tetrapeptide sequence for developing antibacterial agents that are effective against infected wounds while supporting wound healing. Utilizing photochemical synthesis, the green synthesis approach provides an environmentally friendly and sustainable alternative to conventional methods.

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