-
Accounts of Chemical Research Apr 2017The wide range of fascinating supramolecular architectures found in nature, from DNA double helices to giant protein shells, inspires researchers to mimic the diverse... (Review)
Review
The wide range of fascinating supramolecular architectures found in nature, from DNA double helices to giant protein shells, inspires researchers to mimic the diverse shapes and functions of natural systems. Thus, a variety of artificial molecular platforms have been developed by assembling DNA-, peptide-, and protein-based building blocks for medicinal and biological applications. There has also been a significant interest in the research of non-natural oligomers (i.e., foldamers) that fold into well-defined secondary structures analogous to those found in proteins, because the assemblies of foldamers are expected not only to form biomimetic supramolecular architectures that resemble those of nature but also to display unique functions and unprecedented topologies at the same time due to their different folding propensities from those of natural building blocks. Foldamer-based supramolecular architectures have been reported in the form of nanofibers, nanochannels, nanosheets, and finite three-dimensional (3D) shapes. We have developed a new class of crystalline peptidic materials termed "foldectures" (a compound of foldamer and architecture) with unprecedented topological complexity derived from the rapid and nonequilibrium aqueous phase self-assembly of foldamers. In this Account, we discuss the morphological features, molecular packing structures, physical properties, and potential applications of foldectures. Foldectures exhibit well-defined, microscale, homogeneous, and finite structures with unique morphologies such as windmill, tooth, and trigonal bipyramid shapes. The symmetry elements of the morphologies vary with the foldamer building blocks and are retained upon surfactant-assisted shape evolution. Structural characterization by powder X-ray diffraction (PXRD) revealed the molecular packing structures, suggesting how the foldamer building blocks assembled in the 3D structure. The analysis by PXRD showed that intermolecular hydrogen bonding connects foldamers in head-to-tail fashion, while hydrophobic attraction plays a role in arranging foldamers in parallel, antiparallel, or cholesteric phase-like manners. Each packing structure from the foldamer building blocks possesses distinct symmetry elements that are directly expressed in the 3D morphologies. Because of their well-ordered molecular packing structures, foldectures exhibit facet-dependent surface characteristics and anisotropic magnetic susceptibility. The facet-dependent surface property was harnessed to synthesize anisotropic metal nanoparticle-foldecture composites, and the anisotropic magnetic susceptibility enables foldectures to undergo real-time alignment and rotating motion in response to an external magnetic field. By means of their unusual shapes and properties, foldectures have been demonstrated to mimic the functionality of natural systems such as magnetosomes or carboxysomes. Further development of foldectures using higher-order building units, complicated packing motifs, and functional moieties could provide a novel biocompatible platform rivaling 3D biological architectures in natural systems.
Topics: Magnetospirillum; Models, Molecular; Particle Size; Peptides; Powder Diffraction; Protein Conformation; Protein Folding
PubMed: 28191927
DOI: 10.1021/acs.accounts.6b00545 -
Journal of Chemical Information and... Oct 2023Receptor-selective peptides are widely used as smart carriers for specific tumor-targeted delivery. A remarkable example is the cyclic nonapeptide RGD (CRGDKPGDC, ) that...
Receptor-selective peptides are widely used as smart carriers for specific tumor-targeted delivery. A remarkable example is the cyclic nonapeptide RGD (CRGDKPGDC, ) that couples intrinsic cytotoxic effects with striking tumor-homing properties. These peculiar features are based on a rather complex multistep mechanism of action, where the primary event is the recognition of RGD integrins. Despite the high number of preclinical studies and the recent success of a phase I trial for the treatment of pancreatic ductal adenocarcinoma (PDAC), there is little information available about the RGD three-dimensional (3D) structure and integrin binding properties. Here, we re-evaluate the peptide's affinity for cancer-related integrins including not only the previously known targets αvβ3 and αvβ5 but also the αvβ6 isoform, which is known to drive cell growth, migration, and invasion in many malignancies including PDAC. Furthermore, we use parallel tempering in the well-tempered ensemble (PT-WTE) metadynamics simulations to characterize the in-solution conformation of RGD and extensive molecular dynamics calculations to fully investigate its binding mechanism to integrin partners. Finally, we provide clues for fine-tuning the peptide's potency and selectivity profile, which, in turn, may further improve its tumor-homing properties.
Topics: Integrins; Cell Line, Tumor; Oligopeptides; Peptides; Pancreatic Neoplasms
PubMed: 37788340
DOI: 10.1021/acs.jcim.3c01071 -
Critical Reviews in Therapeutic Drug... 2023In the field of pharmaceutical biotechnology and formulation development, various protein and peptide-based drugs have been used for therapeutic and clinical... (Review)
Review
In the field of pharmaceutical biotechnology and formulation development, various protein and peptide-based drugs have been used for therapeutic and clinical implications. These are mainly given via parenteral routes like intravenous, subcutaneous or intramuscular delivery. Teriparatide, also known as PTH 1-34, is a U.S. Food & Drug Administartion-approved anabolic drug to treat osteoporosis is currently available in market only as subcutaneous injection. The quest for elimination of needle in case of given peptidal delivery to replace it with alternative routes like nasal, buccal, transdermal and pulmonary pathways has driven meticulous drug research. The pharmaceutical scientists are working on innovation and approaches involving new materials and methods to develop the formulations for protein and peptides by noninvasive routes. Lately, various approaches have been carried out which involve many strategies and technologies to deliver teriparatide via alternative routes. But, physicochemical instability, proteolytic degradation, low bioavailability, etc. are some obstacles to develop suitable delivery system for teriparatide. This review intends to gather the overall developments in delivery systems specific to teriparatide which meant for better convenience and avoids vulnerability of multiple subcutaneous injections. In addition, the article emphasizes on the successes to develop noninvasive technologies and devices, and new milestones for teriparatide delivery.
Topics: Humans; Teriparatide; Drug Delivery Systems; Proteins; Peptides; Pharmaceutical Preparations
PubMed: 37585311
DOI: 10.1615/CritRevTherDrugCarrierSyst.2023045480 -
Frontiers in Immunology 2019Lower respiratory infection caused by human pathogens such as influenza and respiratory syncytial virus (RSV) is a significant healthcare burden that must be addressed.... (Review)
Review
Lower respiratory infection caused by human pathogens such as influenza and respiratory syncytial virus (RSV) is a significant healthcare burden that must be addressed. The preferred options to achieve this goal are usually to develop vaccines for prophylaxis and to develop antiviral small molecules to treat infected patients with convenient, orally administrable drugs. However, developing a vaccine against RSV poses special challenges with the diminished immune system of infants and the elderly, and finding a universal flu vaccine is difficult because the product must target a large array of viral strains. On the other hand, the use of small-molecule antivirals can result in the emergence of resistant viruses as it has well-been reported for HIV, influenza, and hepatitis C virus (HCV). This paper reviews peptide antiviral strategies as an alternative to address these challenges. The discovery of influenza and RSV peptidic fusion inhibitors will be discussed and compared to small molecules in view of escape mutations. The importance of constraining peptides into macrocycles to improve both their inhibitory activity and pharmacological properties will be highlighted.
Topics: Antiviral Agents; Humans; Influenza, Human; Peptides; Respiratory Syncytial Virus Infections
PubMed: 31293570
DOI: 10.3389/fimmu.2019.01366 -
Biosensors Mar 2022is infamous for generating hospital-acquired infections, many of which are difficult to treat due to the bacterium's multidrug resistance. A sensitive and robust...
is infamous for generating hospital-acquired infections, many of which are difficult to treat due to the bacterium's multidrug resistance. A sensitive and robust detection method of can help prevent a disease outbreak. Herein, we used cells as bait to screen a commercially available phage-displayed random peptide library for peptides that could be used to detect . The biopanning-derived peptide TSATKFMMNLSP, named KP peptide, displayed a high selectivity for the with low cross-reactivity to related Gram-negative bacteria. The specific interaction between KP peptide and lipopolysaccharide resulted in the peptide's selectivity against . Quantitative analysis of this interaction by enzyme-linked immunosorbent assay revealed that the KP peptide possessed higher specificity and sensitivity toward than commercially available anti- spp. antibodies and could detect at a detection limit of 10 CFU/mL. These results suggest that KP peptide can be a promising alternative to antibodies in developing a biosensor system for detection.
Topics: Anti-Bacterial Agents; Klebsiella pneumoniae; Microbial Sensitivity Tests; Peptides
PubMed: 35323423
DOI: 10.3390/bios12030153 -
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 -
International Journal of Molecular... Apr 2021Technological developments in the field of biologically active peptide applications in medicine have increased the need for new methods for peptide delivery. The...
Technological developments in the field of biologically active peptide applications in medicine have increased the need for new methods for peptide delivery. The disadvantage of peptides as drugs is their low biological stability. Recently, great attention has been paid to self-assembling peptides that can form fibrils. Such a formulation makes bioactive peptides more resistant to enzymatic degradation and druggable. Peptide fibrils can be carriers for peptides with interesting biological activities. These features open up prospects for using the peptide fibrils as long-acting drugs and are a valid alternative to conventional peptidic therapies. In our study, we designed new peptide scaffolds that are a hybrid of three interconnected amino acid sequences and are: pro-regenerative, cleavable by neutrophilic elastase, and fibril-forming. We intended to obtain peptides that are stable in the wound environment and that, when applied, would release a biologically active sequence. Our studies showed that the designed hybrid peptides show a high tendency toward regular fibril formation and are able to release the pro-regenerative sequence. Cytotoxicity studies showed that all the designed peptides were safe, did not cause cytotoxic effects and revealed a pro-regenerative potential in human fibroblast and keratinocyte cell lines. In vivo experiments in a dorsal skin injury model in mice indicated that two tested peptides moderately promote tissue repair in their free form. Our research proves that peptide fibrils can be a druggable form and a scaffold for active peptides.
Topics: Amino Acid Sequence; Animals; Cell Proliferation; Cell Survival; Chemical Phenomena; Drug Carriers; Fibroblasts; Humans; Keratinocytes; Mice; Microscopy, Atomic Force; Microscopy, Electron; Peptides; Proteolysis; Regenerative Medicine; Spectrum Analysis; Tissue Scaffolds; Wound Healing
PubMed: 33917000
DOI: 10.3390/ijms22083818 -
Toxicon : Official Journal of the... Jun 2018Among venomous animals, Hymenoptera have been suggested as a rich source of natural toxins. Due to their broad ecological diversity, venom from Hymenoptera insects... (Review)
Review
Among venomous animals, Hymenoptera have been suggested as a rich source of natural toxins. Due to their broad ecological diversity, venom from Hymenoptera insects (bees, wasps and ants) have evolved differentially thus widening the types and biological functions of their components. To date, insect toxinology analysis have scarcely uncovered the complex composition of bee, wasp and ant venoms which include low molecular weight compounds, highly abundant peptides and proteins, including several allergens. In Hymenoptera, these complex mixtures of toxins represent a potent arsenal of biological weapons that are used for self-defense, to repel intruders and to capture prey. Consequently, Hymenoptera venom components have a broad range of pharmacological targets and have been extensively studied, as promising sources of new drugs and biopesticides. In addition, the identification and molecular characterization of Hymenoptera venom allergens have allowed for the rational design of component-resolved diagnosis of allergy, finally improving the outcome of venom immunotherapy (VIT). Until recently, a limited number of Hymenoptera venoms had been unveiled due to the technical limitations of the approaches used to date. Nevertheless, the application of novel techniques with high dynamic range has significantly increased the number of identified peptidic and proteinaceous toxins. Considering this, the present review summarizes the current knowledge about the most representative Hymenoptera venom peptides and proteins which are under study for a better understanding of the insect-caused envenoming process and the development of new drugs and biopesticides.
Topics: Animals; Arthropod Venoms; Hymenoptera; Insect Proteins; Peptides
PubMed: 29715467
DOI: 10.1016/j.toxicon.2018.04.029 -
Journal of the American Chemical Society Dec 2023Rapid and efficient cyclization methods that form structurally novel peptidic macrocycles are of high importance for medicinal chemistry. Herein, we report the first...
Rapid and efficient cyclization methods that form structurally novel peptidic macrocycles are of high importance for medicinal chemistry. Herein, we report the first gold(I)-catalyzed macrocyclization of peptide-EBXs (ethynylbenziodoxolones) via C-Trp C-H activation. This reaction was carried out in the presence of protecting group free peptide sequences and is enabled by a simple commercial gold catalyst (AuCl·MeS). The method displayed a rapid reaction rate (within 10 min), wide functional group tolerance (27 unprotected peptides were cyclized), and up to 86% isolated yield. The obtained highly conjugated cyclic peptide linker, formed through C-H alkynylation, can be directly applied to live-cell imaging as a fluorescent probe without further attachment of fluorophores.
Topics: Peptides, Cyclic; Peptides; Amino Acid Sequence; Cyclization; Catalysis; Fluorescent Dyes
PubMed: 38035635
DOI: 10.1021/jacs.3c09261 -
ACS Infectious Diseases Jan 2023Using genome mining and heterologous expression, we report the discovery and production of a new antimicrobial lasso peptide from species related to the complex. Using...
Using genome mining and heterologous expression, we report the discovery and production of a new antimicrobial lasso peptide from species related to the complex. Using NMR and mass spectrometric analysis, we show that this lasso peptide, named cloacaenodin, employs a threaded lasso fold which imparts proteolytic resistance that its unthreaded counterpart lacks. Cloacaenodin has selective, low micromolar, antimicrobial activity against species related to the complex, including species implicated in nosocomial infections and against clinical isolates of carbapenem-resistant . We further used site-directed mutagenesis to probe the importance of specific residues to the peptide's biosynthesis, stability, and bioactivity.
Topics: Enterobacter; Anti-Bacterial Agents; Antimicrobial Peptides; Carbapenems; Peptides
PubMed: 36519726
DOI: 10.1021/acsinfecdis.2c00446