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Journal of Peptide Science : An... Aug 2023Membrane-active peptides play an essential role in many living organisms and their immune systems and counter many infectious diseases. Many have dual or multiple... (Review)
Review
Membrane-active peptides play an essential role in many living organisms and their immune systems and counter many infectious diseases. Many have dual or multiple mechanisms and can synergize with other molecules, like peptides, proteins, and small molecules. Although membrane-active peptides have been intensively studied in the past decades and more than 3500 sequences have been identified, only a few received approvals from the US Food and Drug Administration. In this review, we investigated all the peptide therapeutics that have entered the market or were subjected to preclinical and clinical studies to understand how they succeeded. With technological advancement (e.g., chemical modifications and pharmaceutical formulations) and a better understanding of the mechanism of action and the potential targets, we found at least five membrane-active peptide drugs that have entered preclinical/clinical phases and show promising results for cancer treatment. We summarized our findings in this review and provided insights into membrane-active anticancer peptide therapeutics.
Topics: United States; Peptides; Proteins; Pharmaceutical Preparations; Drug Delivery Systems; Drug Compounding
PubMed: 36739581
DOI: 10.1002/psc.3482 -
Advances in Colloid and Interface... Aug 2023The use of small-angle scattering (SAS) in the study of the self-assembly of peptides and peptide conjugates (lipopeptides, polymer-peptide conjugates and others) is... (Review)
Review
The use of small-angle scattering (SAS) in the study of the self-assembly of peptides and peptide conjugates (lipopeptides, polymer-peptide conjugates and others) is reviewed, highlighting selected research that illustrates different methods and analysis techniques. Both small-angle x-ray scattering (SAXS) and small-angle neutron scattering (SANS) are considered along with examples that exploit their unique capabilities. For SAXS, this includes the ability to perform rapid measurements enabling high throughput or fast kinetic studies and measurements under dilute conditions. For SANS, contrast variation using HO/DO mixtures enables the study of peptides interacting with lipids and TR-SANS (time-resolved SANS) studies of exchange kinetics and/or peptide-induced structural changes. Examples are provided of studies measuring form factors of different self-assembled structures (micelles, fibrils, nanotapes, nanotubes etc) as well as structure factors from ordered phases (lyotropic mesophases), peptide gels and hybrid materials such as membranes formed by mixing peptides with polysaccharides or peptide/liposome mixtures. SAXS/WAXS (WAXS: wide-angle x-ray scattering) on peptides and peptide hybrids is also discussed, and the review concludes with a perspective on potential future directions for research in the field.
Topics: Scattering, Small Angle; Kinetics; X-Ray Diffraction; Peptides; Nanostructures
PubMed: 37473606
DOI: 10.1016/j.cis.2023.102959 -
Accounts of Chemical Research Mar 2024There is considerable recent interest in the synthesis and development of peptide-based materials as mimics of natural biological assemblies that utilize proteins and... (Review)
Review
There is considerable recent interest in the synthesis and development of peptide-based materials as mimics of natural biological assemblies that utilize proteins and peptides to form organized structures and develop beneficial properties. Due to their potential compatibility with living organisms, synthetic peptide materials are also being developed for applications such as cell grafting, therapeutic delivery, and implantable diagnostic devices. One desirable feature for such applications is the ability to design materials that can respond to stimuli by changes in their structure or properties under biologically relevant conditions. Peptide and protein assemblies can respond to stimuli, such as changes in temperature, solution pH, ions present in media, or interactions with other biomacromolecules. An exciting area of emerging research is focused on how biology uses the chemistry of sulfur-containing amino acids as a means to regulate biological processes. These concepts have been utilized and expanded in recent years to enable the development of peptide materials with readily switchable properties.The incorporation of sulfur atoms in polypeptides, peptides, and proteins provides unique sites that can be used to alter the physical and biological properties of these materials. Sulfur-containing amino acid residues, most often cysteine and methionine, are able to undergo a variety of selective chemical and enzyme-mediated reactions, which can be broadly characterized as redox or alkylation processes. These reactions often proceed under physiologically relevant conditions, can be reversible, and are significant in that they can alter residue polarity as well as conformations of peptide chains. These sulfur-based reactions are able to switch molecular and macromolecular properties of peptides and proteins in living systems and recently have been applied to synthetic peptide materials. Naturally occurring "sulfur switches" can be reversible or irreversible and are often triggered by enzymatic activity. Sulfur switches in peptide materials can also be triggered using oxidation/reduction and alkylation as well as photochemical reactions. The application of sulfur switches to peptide materials has greatly expanded the scope of these switches due to the ability to readily incorporate a wide variety of noncanonical sulfur-containing synthetic amino acids.Sulfur switches have been shown to provide considerable potential to reversibly alter peptide material properties under mild physiologically relevant conditions. An important molecular feature of sulfur-containing amino acid residues was found to be the location of sulfur atoms in the side chains. The variation of sulfur atom positions from the backbone by single bond lengths was found to significantly affect polypeptide chain conformations upon oxidation-reduction or alkylation/dealkylation reactions. With the successful adaptation of sulfur switches to peptide materials, future studies can explore how these switches affect how these materials interact with biological systems. This Account provides an overview of the different types of sulfur switch reactions found in biology and their properties and the elaboration of these switches in synthetic systems with a focus on recent developments and applications of reversible sulfur switches in peptide materials.
Topics: Amines; Amino Acids; Cysteine; Peptides; Proteins; Sulfur
PubMed: 38373227
DOI: 10.1021/acs.accounts.3c00626 -
Journal of Dental Research Dec 2023Biomimetic strategies like peptide-guided collagen mineralization promise to enhance the effectiveness of dentin remineralization. We recently reported that rationally...
Biomimetic strategies like peptide-guided collagen mineralization promise to enhance the effectiveness of dentin remineralization. We recently reported that rationally designed amelogenin-derived peptides P26 and P32 promoted apatite nucleation, mineralized collagen, and showed potential in enamel regrowth and dentin remineralization. To facilitate the clinical application of amelogenin-derived peptides and to uncover their effectiveness in repairing dentin, we have now implemented a chitosan (CS) hydrogel for peptide delivery and have investigated the effects of P26-CS and P32-CS hydrogels on dentin remineralization using 2 in situ experimental models that exhibited different levels of demineralization. The efficacy of the peptide-CS hydrogels in dentin repair was evaluated by characterizing the microstructure, mineral density, mineral phase, and nanomechanical properties of the remineralized samples. The new strategy of atomic force microscopy PeakForce quantitative nanomechanical mapping was used for direct visualization and nanomechanical analysis of repaired dentin lesions across the lesion depth. Results from the 2 models indicated the potential triple functions of peptide-CS hydrogels for dentin repair: building a highly organized protective mineralized layer on dentin, occluding dentinal tubules by peptide-guided in situ mineralization, and promoting biomimetic dentinal collagen remineralization. Importantly, peptides released from the CS hydrogel could diffuse into the dentinal matrix and penetrate the dentinal tubules, leading to both surface and subsurface remineralization and tubule occlusion. Given our previous findings on peptide-CS hydrogels' potential for remineralizing enamel, we see further promise for hydrogels to treat tooth defects involving multiple hard tissues, as in the case of noncarious cervical lesions.
Topics: Amelogenin; Chitosan; Collagen; Dentin; Hydrogels; Minerals; Peptides; Tooth Remineralization
PubMed: 37880947
DOI: 10.1177/00220345231198228 -
Drug Delivery Dec 2023Peptides, as potential therapeutics continue to gain importance in the search for active substances for the treatment of numerous human diseases, some of which are, to... (Review)
Review
Peptides, as potential therapeutics continue to gain importance in the search for active substances for the treatment of numerous human diseases, some of which are, to this day, incurable. As potential therapeutic drugs, peptides have many favorable chemical and pharmacological properties, starting with their great diversity, through their high affinity for binding to all sort of natural receptors, and ending with the various pathways of their breakdown, which produces nothing but amino acids that are nontoxic to the body. Despite these and other advantages, however, they also have their pitfalls. One of these disadvantages is the very low stability of natural peptides. They have a short half-life and tend to be cleared from the organism very quickly. Their instability in the gastrointestinal tract, makes it impossible to administer peptidic drugs orally. To achieve the best pharmacologic effect, it is desirable to look for ways of modifying peptides that enable the use of these substances as pharmaceuticals. There are many ways to modify peptides. Herein we summarize the approaches that are currently in use, including lipidization, PEGylation, glycosylation and others, focusing on lipidization. We describe how individual types of lipidization are achieved and describe their advantages and drawbacks. Peptide modifications are performed with the goal of reaching a longer half-life, reducing immunogenicity and improving bioavailability. In the case of neuropeptides, lipidization aids their activity in the central nervous system after the peripheral administration. At the end of our review, we summarize all lipidized peptide-based drugs that are currently on the market.
Topics: Peptides; Lipids
PubMed: 38010881
DOI: 10.1080/10717544.2023.2284685 -
Biophysical Journal Jun 2024Diffusion determines the turnover of biomolecules in liquid-liquid phase-separated condensates. We considered the mean square displacement and thus the diffusion...
Diffusion determines the turnover of biomolecules in liquid-liquid phase-separated condensates. We considered the mean square displacement and thus the diffusion constant for simple model systems of peptides GGGGG, GGQGG, and GGVGG in aqueous solutions after phase separation by simulating atomic-level models. These solutions readily separate into aqueous and peptide-rich droplet phases. We noted the effect of the peptides being in a solvated, surface, or droplet state on the peptide's diffusion coefficients. Both sequence and peptide conformational distribution were found to influence diffusion and condensate turnover in these systems, with sequence dominating the magnitude of the differences. We found that the most compact structures for each sequence diffused the fastest in the peptide-rich condensate phase. This model result may have implications for turnover dynamics in signaling systems.
Topics: Diffusion; Peptides; Biomolecular Condensates; Amino Acid Sequence; Water; Models, Molecular; Protein Conformation
PubMed: 38751116
DOI: 10.1016/j.bpj.2024.05.009 -
Current Medicinal Chemistry 2024During the last few decades, several efforts have been made towards developing biocompatible materials. Among them, peptide amphiphiles (PAs) constitute a novel... (Review)
Review
During the last few decades, several efforts have been made towards developing biocompatible materials. Among them, peptide amphiphiles (PAs) constitute a novel nanotechnological strategy used in the field of biomedicine since they can provide tissue- specific binding and localization. PAs possess several regions combining hydrophobic and hydrophilic areas that are able to self-assemble in aqueous media, forming different tertiary nanostructures able to interact with cellular membranes. Moreover, these molecules can be tuned by incorporating collagen, lipids, or fluorescent markers. In addition, they can also be used as carriers in order to encapsulate active compounds for drug delivery showing promising features in this area. In this review, the self-assembled structures of PAs as well as their pharmacological applications have been summarized. Furthermore, their use as drug delivery systems has been highlighted and the latest advances in this field have been reviewed.
Topics: Humans; Pharmaceutical Preparations; Peptides; Nanostructures; Drug Delivery Systems; Biocompatible Materials
PubMed: 37031390
DOI: 10.2174/0929867330666230408203820 -
Chembiochem : a European Journal of... Jul 2023Cyclic peptides are important building blocks for forming functional structures and have been applied in various fields. Considering the significant structural and... (Review)
Review
Cyclic peptides are important building blocks for forming functional structures and have been applied in various fields. Considering the significant structural and functional roles of cyclic peptides in materials science and the attributed biophysical advantages, we provide an overview of cyclic peptide types that can self-assemble to form nanotubes, recent progress in stimuli-triggered cyclic peptide assembly, and methods to construct peptide and polymer conjugates based on cyclic peptides with alternative chirality. Specifically, we highlight the roles that stimuli-triggered cyclic peptides and their conjugates play in biomedical applications. Recent progress in other cyclic peptides acting as gelators in drug delivery and biomedicine are also summarized. These cyclic peptides with self-assembly properties are expected to act as adaptive systems for drug delivery and selective disease targeting.
Topics: Peptides, Cyclic; Peptides; Nanotubes; Polymers; Drug Delivery Systems
PubMed: 37017003
DOI: 10.1002/cbic.202300018 -
Diabetes Sep 2023The family of proglucagon peptides Includes glucagon and glucagon-like peptide 1 (GLP-1), two unique peptides derived from the same prohormone. Despite numerous...
The family of proglucagon peptides Includes glucagon and glucagon-like peptide 1 (GLP-1), two unique peptides derived from the same prohormone. Despite numerous similarities between the peptides, these have long been viewed as having opposing actions on metabolism. GLP-1 is described as a postprandial hormone that stimulates anabolic actions via insulin, while glucagon is viewed as a fasting hormone that drives catabolic actions to maintain euglycemia. Here, we revisit a classic article in Diabetes that first established that glucagon and GLP-1 have more in common than previously appreciated, including actions at the same receptor. Furthermore, we discuss how the impact of this observation has guided research decades later that has reshaped the view of how proglucagon hormones regulate metabolism.
Topics: Glucagon; Proglucagon; Insulin; Glucagon-Like Peptide 1; Fasting
PubMed: 37603722
DOI: 10.2337/dbi23-0014 -
ACS Infectious Diseases Apr 2024Pathogenic bacteria cause the deaths of millions of people every year. With the development of antibiotics, hundreds and thousands of people's lives have been saved.... (Review)
Review
Pathogenic bacteria cause the deaths of millions of people every year. With the development of antibiotics, hundreds and thousands of people's lives have been saved. Nevertheless, bacteria can develop resistance to antibiotics, rendering them insensitive to antibiotics over time. Peptides containing specific amino acids can be used as antibacterial agents; however, they can be easily degraded by proteases . To address these issues, branched peptide dendrimers are now being considered as good antibacterial agents due to their high efficacy, resistance to protease degradation, and low cytotoxicity. The ease with which peptide dendrimers can be synthesized and modified makes them accessible for use in various biological and nonbiological fields. That is, peptide dendrimers hold a promising future as antibacterial agents with prolonged efficacy without bacterial resistance development. Their stability and multivalence allow them to effectively target multi-drug-resistant strains and prevent biofilm formation. Thus, it is interesting to have an overview of the development and applications of peptide dendrimers in antibacterial research, including the possibility of employing machine learning approaches for the design of AMPs and dendrimers. This review summarizes the synthesis and applications of peptide dendrimers as antibacterial agents. The challenges and perspectives of using peptide dendrimers as the antibacterial agents are also discussed.
Topics: Humans; Anti-Bacterial Agents; Dendrimers; Peptides; Bacteria
PubMed: 38428037
DOI: 10.1021/acsinfecdis.3c00624