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Bioorganic & Medicinal Chemistry Jun 2018The development of solid phase peptide synthesis has released tremendous opportunities for using synthetic peptides in medicinal applications. In the last decades,... (Review)
Review
The development of solid phase peptide synthesis has released tremendous opportunities for using synthetic peptides in medicinal applications. In the last decades, peptide therapeutics became an emerging market in pharmaceutical industry. The need for synthetic strategies in order to improve peptidic properties, such as longer half-life, higher bioavailability, increased potency and efficiency is accordingly rising. In this mini-review, we present a toolbox of modifications in peptide chemistry for overcoming the main drawbacks during the transition from natural peptides to peptide therapeutics. Modifications at the level of the peptide backbone, amino acid side chains and higher orders of structures are described. Furthermore, we are discussing the future of peptide therapeutics development and their impact on the pharmaceutical market.
Topics: Animals; Chemistry Techniques, Synthetic; Drug Discovery; Humans; Lipids; Models, Molecular; Peptides; Polyethylene Glycols; Polymers; Solid-Phase Synthesis Techniques
PubMed: 29395804
DOI: 10.1016/j.bmc.2018.01.012 -
Chemical Society Reviews Mar 2021Coacervates are condensed liquid-like droplets formed by liquid-liquid phase separation of molecules through multiple weak associative interactions. In recent years it... (Review)
Review
Coacervates are condensed liquid-like droplets formed by liquid-liquid phase separation of molecules through multiple weak associative interactions. In recent years it has emerged that not only long polymers, but also short peptides are capable of forming simple and complex coacervates. The coacervate droplets they form act as compartments that sequester and concentrate a wide range of solutes, and their spontaneous formation make coacervates attractive protocell models. The main advantage of peptides as building blocks lies in the functional diversity of the amino acid residues, which allows for tailoring of the peptide's phase separation propensity, their selectivity in guest molecule uptake and the physicochemical and catalytic properties of the compartments. The aim of this tutorial review is to illustrate the recent developments in the field of peptide-based coacervates in a systematic way and to deduce the basic requirements for both simple and complex coacervation of peptides. We review a selection of peptide coacervates that illustrates the essentials of phase separation, the limitations, and the properties that make peptide coacervates biomimetic protocells. Finally, we provide some perspectives of this novel research field in the direction of active droplets, moving away from thermodynamic equilibrium.
Topics: Artificial Cells; Biomimetics; Catalysis; Nucleotides; Peptides; Polyethylene Glycols
PubMed: 33616129
DOI: 10.1039/d0cs00307g -
Journal of Peptide Science : An... Jan 2023Protein-protein interactions (PPI) are involved in all cellular processes and many represent attractive therapeutic targets. However, the frequently rather flat and... (Review)
Review
Protein-protein interactions (PPI) are involved in all cellular processes and many represent attractive therapeutic targets. However, the frequently rather flat and large interaction areas render the identification of small molecular PPI inhibitors very challenging. As an alternative, peptide interaction motifs derived from a PPI interface can serve as starting points for the development of inhibitors. However, certain proteins remain challenging targets when applying inhibitors with a competitive mode of action. For that reason, peptide-based ligands with an irreversible binding mode have gained attention in recent years. This review summarizes examples of covalent inhibitors that employ peptidic binders and have been tested in a biological context.
Topics: Peptides
PubMed: 36239115
DOI: 10.1002/psc.3457 -
Langmuir : the ACS Journal of Surfaces... Nov 2022The safe and efficient delivery of nucleic acids including DNA, mRNA, siRNA, and miRNA into targeted cells is critical for gene therapy. Currently, viral gene vectors... (Review)
Review
The safe and efficient delivery of nucleic acids including DNA, mRNA, siRNA, and miRNA into targeted cells is critical for gene therapy. Currently, viral gene vectors are very popular, but they have potential toxicity and insecurity. Therefore, the development of nonviral vectors has attracted considerable research attention. Peptide assemblies are superior candidates for being used as gene vectors by having good biocompatibility, versatile molecular design, excellent assembly capacity, ease of modification, and stimuli responsivity. The de novo designed peptides not only can induce efficient condensation of nucleic acids into compacted nanoparticles and protect them from enzymatic digestion but also can effectively overcome biological barriers and improve gene delivery efficiency through targeted delivery, enhanced cellular uptake, improved endolysosomal escape, and nuclear importation. By having these merits, peptidic gene vectors are developing fast, showing outstanding advantages compared to liposome and polymer vectors. This Perspective focuses on peptidic gene delivery systems by emphasizing the molecular design strategies for meeting the criteria of gene condensation, protection from nuclease degradation, cellular uptake, endolysosomal escape, and so on. The new arising research area of peptide-based artificial viruses for gene and ribonucleoprotein delivery has also been reviewed. The challenges and future perspectives are put forward, aiming to provide a conclusive guide for the development of peptidic delivery systems to achieve efficient gene therapy.
Topics: Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Nucleic Acids; Peptides
PubMed: 36318179
DOI: 10.1021/acs.langmuir.2c02197 -
Mass Spectrometry Reviews Sep 2017Most methods for interpreting data from shotgun proteomics experiments are to large degree dependent on being able to predict properties of peptide-ions. Often such... (Review)
Review
Most methods for interpreting data from shotgun proteomics experiments are to large degree dependent on being able to predict properties of peptide-ions. Often such predicted properties are limited to molecular mass and fragment spectra, but here we put focus on a perhaps underutilized property, a peptide's chromatographic retention time. We review a couple of different principles of retention time prediction,and their applications within computational proteomics. © 2016 Wiley Periodicals, Inc. Mass Spec Rev 36:615-623, 2017.
Topics: Chromatography, Reverse-Phase; Computational Biology; Machine Learning; Peptides; Proteomics; Time Factors
PubMed: 26799864
DOI: 10.1002/mas.21488 -
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 -
Journal of Peptide Science : An... May 1998Siderophores are low molecular weight iron chelators, produced by virtually all bacteria, fungi and some plants. They serve to deliver the essential element iron, barely... (Review)
Review
Siderophores are low molecular weight iron chelators, produced by virtually all bacteria, fungi and some plants. They serve to deliver the essential element iron, barely soluble under aerobic conditions, into microbial cells. Siderophores are therefore important secondary metabolites which are very often based on amino acids and their derivatives. Biosynthesis, transport, regulation and chemical synthesis of natural siderophores and their analogues is of considerable interest for the protein and peptide chemist. This review gives an overview of the structural classes of peptidic siderophores, along with data on their biosynthesis. On a number of representative examples, strategies and schemes of their chemical synthesis are described.
Topics: Amino Acid Sequence; Amino Acids; Molecular Sequence Data; Peptides; Protein Conformation; Siderophores
PubMed: 9643626
DOI: 10.1002/(SICI)1099-1387(199805)4:3%3C147::AID-PSC136%3E3.0.CO;2-C -
Advances in Protein Chemistry and... 2015Knowledge of the sequences and structures of proteins from pathogenic microorganisms has been put to great use in the field of protein chemistry for the development of... (Review)
Review
Knowledge of the sequences and structures of proteins from pathogenic microorganisms has been put to great use in the field of protein chemistry for the development of peptide-based vaccines. These vaccine constructs include chemically tailored, shorter peptidic fragments that can induce high immunogenicity, thus shunning the allergenic and nonimmunogenic part of the antigens. Based on this concept, several different chemistries have been pursued to obtain novel platforms onto which antigenic epitopes can be tethered, with the aim to achieve a higher antibody response. In this regard, here we attempt to summarize the chemical strategies developed for the presentation of peptide epitopes.
Topics: AIDS Vaccines; HIV; Influenza Vaccines; Orthomyxoviridae; Peptides; Vaccines, Synthetic
PubMed: 26067818
DOI: 10.1016/bs.apcsb.2015.03.005 -
ACS Nano May 2023Vitiligo, a common skin disease that seriously affects 0.5-2.0% of the worldwide population, lacks approved therapeutics due to a wide range of adverse side effects. As...
Vitiligo, a common skin disease that seriously affects 0.5-2.0% of the worldwide population, lacks approved therapeutics due to a wide range of adverse side effects. As a key regulator of skin pigmentation, MC1R may be an effective therapeutic target for vitiligo. Herein, we report an MC1R peptide agonist that directly self-assembles into nanofibrils that form a hydrogel matrix under normal physiological conditions. This hydrogel exhibits higher stability than free peptides, sustained release, rapid recovery from shear-thinning, and resistance to enzymatic proteolysis. Furthermore, this peptidal MC1R agonist upregulates tyrosinase, tyrosinase-related protein-1 (TYRP-1), and tyrosinase-related protein-2 (TYRP-2) to stimulate melanin synthesis. More importantly, MC1R agonist hydrogel promotes skin pigmentation in mice more potently than free MC1R agonist. This study supports the development of this MC1R agonist hydrogel as a promising pharmacological intervention for vitiligo.
Topics: Animals; Mice; Skin Pigmentation; Vitiligo; Hydrogels; Receptor, Melanocortin, Type 1; Peptides; Pigmentation
PubMed: 37115703
DOI: 10.1021/acsnano.3c01960 -
Nature Chemical Biology Dec 2013Specific immune responses are critically dependent on protein degradation products in the form of peptides. These peptides are presented by major histocompatibility... (Review)
Review
Specific immune responses are critically dependent on protein degradation products in the form of peptides. These peptides are presented by major histocompatibility complexes (MHCs), and recognition of MHC-peptide complexes by the immune system determines successful pathogen elimination, transplant rejection, autoimmunity or death. Here we review the immune response from the peptide's perspective and discuss the fate of peptides in cells before presentation by MHC complexes. We then discuss how peptides are altered post-translationally to yield immune responses and how peptides can be engineered to achieve strong immune responses following vaccination. Although peptides are simple from a chemical perspective, they are complex in their immunological consequences.
Topics: Animals; Antigens; Major Histocompatibility Complex; Models, Molecular; Peptides; Protein Conformation; Protein Subunits
PubMed: 24231618
DOI: 10.1038/nchembio.1391