1,720,987 research outputs found
Lasso Peptides Realm: Insights and Applications
Get PDFLasso peptides exhibit a range of bioactivities, including antiviral effects, inhibition of the glucagon receptor, blockade of the endothelin type B receptor, inhibition of myosin light chain kinase, and modulation of the atrial natriuretic factor, as well as notable antimicrobial properties. Intriguingly, lasso peptides exhibit remarkable proteolytic and thermal stability, addressing one of the key challenges that traditional peptides often face. The challenge in producing those valuable peptides remains the main hurdle in the way of producing larger quantities or even modifying them with more potent analogues. Genome mining and heterologous expression approaches have greatly facilitated the production of lasso peptides, moving beyond mere isolation techniques. This advancement not only allows for larger quantities but also enables the creation of additional analogues with improved stability and potency. This review aims to explore the unique bioactivities and stability of lasso peptides, along with recent advancements in genome mining and heterologous expression that address production challenges and open pathways for engineering potent analogues
FDA-Approved Antibacterials and Echinocandins
Get PDFSince 1955, a total of 12 peptide-based drugs with antimicrobial or antifungal properties have received approval from the Food and Drug Administration (FDA). Peptides present a promising opportunity to address serious infections that may be challenging to manage through other means. Peptides exhibit the capability to leverage various mechanisms, and in some cases, multiple mechanisms are employed for this purpose. Despite the initial approval dating back to 1955, the FDA recently approved an echinocandin peptide just last year. The ongoing approvals underscore the significance of peptides in addressing ongoing medical challenges. Approximately 22 peptide therapeutics with an antibacterial and antifungal spectrum are currently undergoing various phases of clinical trials, showing promising results. In this review, antimicrobial and antifungal peptides are analyzed in terms of their chemical structure, indication, mode of action, and development journey, concluding with their arrival in the pharmaceutical market
Exploring FDA-Approved Frontiers: Insights into Natural and Engineered Peptide Analogues in the GLP-1, GIP, GHRH, CCK, ACTH, and α-MSH Realms
Get PDFPeptides continue to gain significance in the pharmaceutical arena. Since the unveiling of insulin in 1921, the Food and Drug Administration (FDA) has authorised around 100 peptides for various applications. Peptides, although initially derived from endogenous sources, have evolved beyond their natural origins, exhibiting favourable therapeutic effectiveness. Medicinal chemistry has played a pivotal role in synthesising valuable natural peptide analogues, providing synthetic alternatives with therapeutic potential. Furthermore, key chemical modifications have enhanced the stability of peptides and strengthened their interactions with therapeutic targets. For instance, selective modifications have extended their half-life and lessened the frequency of their administration while maintaining the desired therapeutic action. In this review, I analyse the FDA approval of natural peptides, as well as engineered peptides for diabetes treatment, growth-hormone-releasing hormone (GHRH), cholecystokinin (CCK), adrenocorticotropic hormone (ACTH), and α-melanocyte stimulating hormone (α-MSH) peptide analogues. Attention will be paid to the structure, mode of action, developmental journey, FDA authorisation, and the adverse effects of these peptides
Unlocking the Potential of Retro-Inverso (RI) Peptides as Future Drug Candidates
Get PDFBackgroundWith the rising demand for peptide-based drugs, enhancing their stability against proteolytic degradation has become a critical challenge. Strategies to improve peptide stability include cyclization, substitution of L-amino acids with D-amino acids, incorporation of β-amino acids, and various formulation techniques. An innovative approach involves modifying the peptide backbone by reversing the amide bond direction and inverting the stereochemistry of amino acids in the same segment. This approach results in the formation of retro-inverso peptides, which offer increased stability, permeability, and cellular uptake.PurposeThe aim of this review is to provide a comprehensive analysis of retro-inverso peptides, focusing on their concept, synthesis, and applications as potential therapeutic agents, drug delivery systems, and in aesthetic applications.MethodsThe review explores the theoretical underpinnings of retro-inverso peptide design and its application to both linear and cyclic peptides. The synthesis strategies of retro-inverso peptides are discussed in detail, along with their formulation and practical utility in various biomedical fields.ResultsRetro-inverso peptides show promise in enhancing peptide stability and improving biological properties such as permeability and cellular uptake. Their unique structure offers advantages in drug development and potential as therapeutic agents or drug carriers.ConclusionRetro-inverso peptides represent a valuable strategy for overcoming the limitations of conventional peptides, especially regarding stability and bioavailability. This review highlights their potential in therapeutic development and other applications, reinforcing the importance of continued research and innovation in peptide chemistry
FDA\u27s stamp of approval: Unveiling peptide breakthroughs in cardiovascular diseases, ACE, HIV, CNS, and beyond
Get PDFPeptides exhibit significant specificity and effective interaction with therapeutic targets, positioning themselves as key players in the global pharmaceutical market. They offer potential treatments for a wide range of diseases, including those that pose significant challenges. Notably, the peptide trofinetide (Daybue) marked a groundbreaking achievement by providing the first-ever cure for Rett syndrome, and several peptides have secured FDA approval as first-in-class medications. Furthermore, peptides are expanding their presence in areas traditionally dominated by either small or large molecules. A noteworthy example is the FDA approval of motixafortide (Aphexda) as the first peptide-based chemokine antagonist. Here, the focus will be on the analysis of FDA-approved peptides, particularly those targeting cardiovascular diseases, human immunodeficiency, central nervous system diseases, and various other intriguing classes addressing conditions such as osteoporosis, thrombocytopenia, Cushing\u27s disease, and hypoglycemia, among others. The review will explore the chemical structures of the peptides, their indications and modes of action, the developmental trajectory, and potential adverse effects
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Oligonucleotides: evolution and innovation
Get PDFOligonucleotides, comprising single or double strands of RNA or DNA, are vital chemical compounds used in various laboratory and clinical applications. They represent a significant class of therapeutics with a rapidly expanding range of uses. Between 1998 and 2023, 19 oligonucleotides have received approval from the U.S. Food and Drug Administration (FDA). Their synthesis methods have undergone significant evolution over time. This review examines several oligonucleotide synthesis techniques, including phosphodiester, phosphotriester, and phosphoramidite approaches. It begins with a discussion of an early synthesis method involving a phosphoryl chloride intermediate, which proved unstable and prone to hydrolysis. The review then transitions to the solid-phase synthesis method, which uses polymer resins as a solid support, emphasizing its advantages over both phosphotriester and phosphoramidite techniques. This is followed by an exploration of recent advancements in oligonucleotide enzymatic synthesis, concluding with a discussion on modifications to bases, sugars, and backbones designed to improve their properties and therapeutic potential
Peptide Therapeutics: Unveiling the Potential against Cancer—A Journey through 1989
Get PDFThe United States Food and Drug Administration (FDA) has approved a plethora of peptide-based drugs as effective drugs in cancer therapy. Peptides possess high specificity, permeability, target engagement, and a tolerable safety profile. They exhibit selective binding with cell surface receptors and proteins, functioning as agonists or antagonists. They also serve as imaging agents for diagnostic applications or can serve a dual-purpose as both diagnostic and therapeutic (theragnostic) agents. Therefore, they have been exploited in various forms, including linkers, peptide conjugates, and payloads. In this review, the FDA-approved prostate-specific membrane antigen (PSMA) peptide antagonists, peptide receptor radionuclide therapy (PRRT), somatostatin analogs, antibody–drug conjugates (ADCs), gonadotropin-releasing hormone (GnRH) analogs, and other peptide-based anticancer drugs are analyzed in terms of their chemical structures and properties, therapeutic targets and mechanisms of action, development journey, administration routes, and side effects
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
- …
