Current Pharmaceutical Design - Volume 28, Issue 44, 2022

The antimicrobial peptide (AMP) is a class of molecules that are active against a variety of microorganisms, from bacterial and cancer cells to fungi. Most AMPs are natural products, as part of an organism's own defense system against harmful microbes. However, the growing prevalence of drug resistance has forced researchers to design more promising engineered antimicrobial agents. Inspired by the amphiphilic detergents, the hydrophobic-hydrophilic alternation pattern was considered to be a simple but effective way to de novo design AMPs. In this model, hydrophobic amino acids (leucine, isoleucine etc.) and hydrophilic amino acids (arginine, lysine etc.) were arranged in an alternating way in the peptide sequence. The majority of this type of peptides have a clear hydrophilic-hydrophobic interface, which allows the molecules to have good solubility in both water and organic solvents. When they come into contact with hydrophobic membranes, many peptides undergo a conformational transformation, facilitating themself to insert into the cellular envelope. Moreover, positive-charged peptide amphiphiles tended to have an affinity with negatively-charged membrane interfaces and further led to envelope damage and cell death. Herein, several typical design patterns have been reviewed. Though varying in amino acid sequence, they all basically follow the rule of alternating arrangement of hydrophilic and hydrophobic residues. Based on that, researchers synthesized some lead compounds with favorable antimicrobial activities and preliminarily investigated their possible mode of action. Besides membrane disruption, these AMPs are proven to kill microbes in multiple mechanisms. These results deepened our understanding of AMPs’ design and provided a theoretical basis for constructing peptide candidates with better biocompatibility and therapeutic potential.

Global dissemination of antimicrobial resistance (AMR) not only poses a significant threat to human health, food security, and social development but also results in millions of deaths each year. In Gram-negative bacteria, the primary mechanism of resistance to β-lactam antibiotics is the production of β-lactamases, one of which is carbapenem-hydrolyzing β-lactamases known as carbapenemases. As a general scheme, these enzymes are divided into Ambler class A, B, C, and D based on their protein sequence homology. Class B β-lactamases are also known as metallo-β-lactamases (MBLs). The incidence of recovery of bacteria expressing metallo-β- lactamases (MBLs) has increased dramatically in recent years, almost reaching a pandemic proportion. MBLs can be further divided into three subclasses (B1, B2, and B3) based on the homology of protein sequences as well as the differences in zinc coordination. The development of inhibitors is one effective strategy to suppress the activities of MBLs and restore the activity of β-lactam antibiotics. Although thousands of MBL inhibitors have been reported, none have been approved for clinical use. This review describes the clinical application potential of peptide-based drugs that exhibit inhibitory activity against MBLs identified in past decades. In this report, peptide-based inhibitors of MBLs are divided into several groups based on the mode of action, highlighting compounds of promising properties that are suitable for further advancement. We discuss how traditional computational tools, such as in silico screening and molecular docking, along with new methods, such as deep learning and machine learning, enable a more accurate and efficient design of peptide-based inhibitors of MBLs.

A series of functional biomaterials with different sizes and morphologies can be constructed through self-assembly, among which amphiphilic peptide-based materials have received intense attention. One main possible reason is that the short amphiphilic peptides can facilitate the formation of versatile materials and promote their further applications in different fields. Another reason is that the simple structure of amphiphilic peptides can help establish the structure-function relationship. This review highlights the recent advances in the self-assembly of two typical peptide species, surfactant-like peptides (SLPs) and peptides amphiphiles (PAs). These peptides can self-assemble into diverse nanostructures. The formation of these different nanostructures resulted from the delicate balance of varied non-covalent interactions. This review embraced each non-covalent interaction and then listed the typical routes for regulating these non-covalent interactions, then realized the morphologies modulation of the self-assemblies. Finally, their applications in some biomedical fields, such as the stabilization of membrane proteins, templating for nanofabrication and biomineralization, acting as the antibacterial and antitumor agents, hemostasis, and synthesis of melanin have been summarized. Further advances in the self-assembly of SLPs and PAs may focus on the design of functional materials with targeted properties and exploring their improved properties.

Background: LncRNAs have been reported to be involved in a variety of biological functions, including gene expression, cell growth, and differentiation. They may also serve as oncogenes or tumor suppressor genes in diseases. lncRNAs that can encode small nucleolar RNAs (snoRNAs) have been named small nucleolar RNA host genes (SNHGs). Objective: In this review article, we readily review the regulatory mechanisms and clinical significance of Lnc SNHG4 in cancer. Methods: We systematically investigated databases, like Scopus, PubMed, Embase, Google Scholar, and Cochrane Library database for all research articles, and have provided an overview regarding the biological functions and mechanisms of lncRNA SNHG4 in tumorigenesis. Results: Compared to neighboring normal tissues, SNHG4 is significantly dysregulated in various tumor tissues. SNHG4 upregulation is mainly associated with advanced tumor stage, tumor size, TNM stage, and decreased overall survival. In addition, aberrant SNHG4 expression promotes cell proliferation, metastasis, migration, and invasion of cancer cells. Conclusion: SNHG4 may serve as a new therapeutic target and prognostic biomarker in patients with cancer.

The graphene family nanomaterials (GFNs) have been recognized to have potential applications in biomedicine, especially in the rag nostic, drug delivery and neuroimaging. Multiple studies have examined the neurotoxicity of GFNs to assay their toxic effects on organisms and ecosystems. In this article, we reviewed the different neurotoxicity effects of GFNs at intracellular levels, including nucleus-related effects and cytosolic mechanisms, as well as extracellular levels, including effects on enzyme activity, oxidative stress, behavior, neurotransmitters, and central nervous system (CNS). Furthermore, for the sake of the solution, we discussed the reducing ways of graphene toxicity. A schematic description is shown in Fig. (1).