Progress in molecular biology and translational science最新文献

{"title":"Oral delivery of protein and peptide therapeutics.","authors":"Vivek P Chavda, Pankti C Balar","doi":"10.1016/bs.pmbts.2024.11.003","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.11.003","url":null,"abstract":"<p><p>Oral administration of proteins and peptides has gained significant attention recently due to its potential to transform therapeutic strategies, providing a non-invasive and patient-friendly method for delivering biopharmaceuticals. The primary hurdle in oral delivery stems from the harsh conditions of the gastrointestinal (GI) tract, characterized by acidic pH, enzymatic degradation, and limited permeability across the intestinal epithelium. Various innovative approaches have emerged to overcome these challenges, including nanoparticle-based delivery systems, mucoadhesive formulations, and chemical modifications of peptides aimed at improving stability and absorption rates. Nanoparticle-based delivery systems, such as liposomes, polymeric nanoparticles, and solid lipid nanoparticles, hold promise in protecting proteins and peptides from enzymatic degradation while enhancing their bioavailability. These nanoparticles can be tailored to target specific areas within the GI tract, extending drug release and enhancing therapeutic effectiveness. Mucoadhesive formulations utilize polymers like chitosan, alginate, and polyethylene glycol (PEG) derivatives to adhere to GI mucosal surfaces, prolonging residence time and facilitating drug absorption. Chemical modifications, such as PEGylation, glycosylation, and lipidation have been employed to enhance the stability and permeability of proteins and peptides in the GI tract. PEGylation, in particular, has been widely used to extend the circulation half-life and reduce the immunogenicity of therapeutic proteins. Advancements in nanotechnology, especially the development of smart nanocarriers capable of responsive drug release triggered by pH or enzymatic stimuli, show promise in further improving oral delivery of proteins and peptides. The integration of bioinformatics and computational modeling techniques has facilitated the design of novel drug delivery systems with optimized pharmacokinetic profiles. This chapter focuses on the advancements and challenges in the oral delivery of protein and peptide-based drugs, highlighting the innovative strategies being explored to enhance therapeutic outcomes.</p>","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"212 ","pages":"355-387"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vaccines reimagined: The peptide revolution in disease prevention.","authors":"Vivek P Chavda","doi":"10.1016/bs.pmbts.2024.11.002","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.11.002","url":null,"abstract":"<p><p>Peptide-based vaccines have emerged as a promising avenue in the realm of immunization strategies. This chapter provides an overview of the key aspects and advancements in peptide-based vaccine development. Peptides, as fragments of larger proteins, hold the potential to induce targeted immune responses while minimizing off-target effects. We discuss the principles of peptide selection, epitope identification, and delivery platforms, underscoring the importance of rational design to optimize immunogenicity. The integration of computational tools and advanced analytical methods has enabled the refinement of peptide vaccine candidates. Studies on infectious diseases, cancers, and new pathogens showcase the versatility and efficacy of peptide vaccines. As the field progresses, collaborative efforts between researchers, industry, and healthcare systems are essential to bridge the gap from laboratory research to clinical application. The future holds promise for peptide-based vaccines to contribute significantly to disease prevention and therapeutic intervention.</p>","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"212 ","pages":"329-354"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delivery of protein therapeutics and vaccines using their multivalent complexes with synthetic polyelectrolytes.","authors":"Alexander K Andrianov","doi":"10.1016/bs.pmbts.2024.04.005","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.04.005","url":null,"abstract":"<p><p>Clinical applications of protein and peptide-based therapeutics and vaccines are rapidly expanding. However, the development of promising new product candidates is often hindered by unfavorable pharmacokinetic profiles, which necessitate the implementation of drug delivery systems to improve protein stability and bioavailability. Non-covalent modification of proteins with synthetic polyelectrolytes, which relies on the strength of cooperative multivalent interactions, may offer potential advantages. In contrast to commonly employed covalent conjugation or microencapsulation methodologies, this technology offers dynamic protection of the protein thereby minimizing the loss of its biological activity, enabling \"mix-and-match\" formulation approaches, reducing manufacturing costs and simplifying regulatory processes. The range of potential life sciences applications ranges from immunopotentiation and vaccine delivery systems to long-circulating stealth biotherapeutics. This review analyses current technology in the context of intended clinical indications and discusses various synthetic and formulation approaches leading to supramolecular complexation. It evaluates dynamic interactions of complexes with constituents of physiological compartments and attempts to identify critical factors that can affect future advancement of this paradigm-shifting protein delivery technology.</p>","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"212 ","pages":"235-259"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preface.","authors":"","doi":"10.1016/S1877-1173(25)00044-4","DOIUrl":"https://doi.org/10.1016/S1877-1173(25)00044-4","url":null,"abstract":"","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"212 ","pages":"xvii-xviii"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Membrane-active peptides for anticancer therapies.","authors":"Charles H Chen","doi":"10.1016/bs.pmbts.2024.10.005","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.10.005","url":null,"abstract":"<p><p>Membrane-active peptides are found in many living organisms and play a critical role in their immune systems by combating various infectious diseases. These host defense peptides employ multiple mechanisms against different microorganisms and possess unique functions, such as anti-inflammatory and immunomodulatory effects, often working in synergy with other antimicrobial agents. Despite extensive research over the past few decades and the identification of thousands of sequences, only a few have been successfully applied in clinical settings and received approval from the U.S. Food and Drug Administration. In this chapter, we explore all peptide therapeutics that have reached the market, as well as candidates in preclinical and clinical trials, to understand their success and potential applications in cancer therapy. Our findings indicate that at least four membrane-active peptide drugs have progressed to preclinical or clinical phases, dmonstrating promising results for cancer treatment. We summarize our insights in this chapter, highlighting the potential of membrane-active anticancer peptide therapeutics and their applications as targeting ligands in various biomedical fields.</p>","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"212 ","pages":"67-116"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peptides on patrol: Carrier systems for targeted delivery.","authors":"Vivek P Chavda, Joanna Bojarska","doi":"10.1016/bs.pmbts.2024.11.001","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.11.001","url":null,"abstract":"<p><p>The peptide is a small unit of protein that exhibits a diverse range of therapeutic applications, including but not limited to respiratory, inflammatory, oncologic, metabolic and neurological disorders. Peptides also play a significant role in signal transduction in cells. This chapter focuses on the delivery of peptides through the utilization of various carrier molecules, including liposomes, micelles, polymeric nanoparticles, and inorganic materials. These carriers facilitate targeted delivery and site-specific delivery of peptides. Different nanocarriers and therapeutic drug molecules also help with the delivery of peptides. Application to various diseases and different routes of delivery are described in this manuscript, along with current limitations and future prospects.</p>","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"212 ","pages":"129-161"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peptidomimetics design and characterization: Bridging experimental and computer-based approaches.","authors":"Alice Romagnoli, Jesmina Rexha, Nunzio Perta, Samuele Di Cristofano, Noemi Borgognoni, Gloria Venturini, Francesco Pignotti, Domenico Raimondo, Tiziana Borsello, Daniele Di Marino","doi":"10.1016/bs.pmbts.2024.07.002","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.07.002","url":null,"abstract":"<p><p>Peptidomimetics, designed to mimic peptide biological activity with more drug-like properties, are increasingly pivotal in medicinal chemistry. They offer enhanced systemic delivery, cell penetration, target specificity, and protection against peptidases when compared to their native peptide counterparts. Already utilized in treating diverse diseases like neurodegenerative disorders, cancer and infectious diseases, their future in medicine seems bright, with many peptidomimetics in clinical trials or development stages. Peptidomimetics are well-suited for addressing disturbed protein-protein interactions (PPIs), which often underlie various pathologies. Structural biology and computational methods like molecular dynamics simulations facilitate rational design, whereas machine learning algorithms accelerate protein structure prediction, enabling efficient drug development. Experimental validation via various spectroscopic, biophysical, and biochemical assays confirms computational predictions and guides further optimization. Peptidomimetics, with their tailored constrained structures, represent a frontier in drug design focused on targeting PPIs. In this overview, we present a comprehensive landscape of peptidomimetics, encompassing perspectives on involvement in pathologies, chemical strategies, and methodologies for their characterization, spanning in silico, in vitro and in cell approaches. With increasing interest from pharmaceutical sectors, peptidomimetics hold promise for revolutionizing therapeutic approaches, marking a new era of precision drug discovery.</p>","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"212 ","pages":"279-327"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Daptomycin: Mechanism of action, mechanisms of resistance, synthesis and structure-activity relationships.","authors":"Scott D Taylor, Ryan Moreira","doi":"10.1016/bs.pmbts.2024.04.003","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.04.003","url":null,"abstract":"<p><p>Daptomycin is a cyclic lipodepsipeptide antibiotic that is a mainstay for the treatment of serious infections caused by Gram-positive bacteria, including methicillin-resistant Streptococcus aureus and vancomycin resistant enterococci. It is one of the so-called last-resort antibiotics that are used to tackle life-threatening infections that do not respond to first-line treatments. However, resistance to daptomycin is eroding its clinical efficacy motivating the design and/or discovery of analogues that overcome resistance. The strategy of antibiotic analogue synthesis has been used to overcome bacterial resistance to many classes of antibiotics such as the β-lactams. Pursuing this strategy with daptomycin requires a detailed understanding of daptomycin's action mechanism and synthesis. Here, we discuss the action mechanism of daptomycin in a holistic manner and expand this discussion to rationalize conferred modes of resistance. Synthetic efforts, both chemical and biological, are discussed in detail and the structure-activity relationship emanating from these works is distilled into a usable model that can guide the design of new daptomycin analogues.</p>","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"212 ","pages":"163-234"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting MYC with protein drugs.","authors":"Jumi A Shin","doi":"10.1016/bs.pmbts.2024.07.001","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.07.001","url":null,"abstract":"<p><p>After cardiovascular disease, cancer is our biggest killer. The \"war on cancer\" officially launched in 1971; despite decades of research and development, our arsenal of drugs against cancer still comprises mainly small molecules. Protein drugs, however, are poised to become the foundation for next-generation drugs that target MYC, a proto-oncogene that encodes the MYC transcription factor involved in the majority of human cancers. Such protein drugs work inside the cell in the nucleus, where they interact directly with the genome or can partner with MYC to blunt its detrimental activities. No small-molecule drug has been successful against MYC, but protein drug Omomyc has successfully inhibited solid tumors in human trials. Although MYC is a key regulator of normal cellular processes, we need to develop new tactics to contain MYC when it goes rogue.</p>","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"212 ","pages":"1-23"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surface modified proteins and peptides for targeted drug delivery.","authors":"Vivek P Chavda, Disha Joshi","doi":"10.1016/bs.pmbts.2024.12.001","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.12.001","url":null,"abstract":"<p><p>Surface modification of proteins and peptides has emerged as a promising strategy to enhance their therapeutic efficacy and target specificity. This chapter delves into the various techniques employed to modify the surface properties of these biomolecules, including chemical conjugation, site-specific mutagenesis, and peptide synthesis. The focus is on strategies that improve drug delivery to specific target sites, such as tumor cells or inflamed tissues. By modifying surface properties, it is possible to enhance drug stability, reduce immunogenicity, and prolong circulation time. This chapter explores the latest advancements in this field and discusses the potential applications of surface-modified proteins and peptides in the development of novel therapeutic agents.</p>","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"212 ","pages":"389-438"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}