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Viruses Oct 2013Phage display has become an established, widely used method for selection of peptides, antibodies or alternative scaffolds. The use of phage display for the selection of... (Review)
Review
Phage display has become an established, widely used method for selection of peptides, antibodies or alternative scaffolds. The use of phage display for the selection of antigens from genomic or cDNA libraries of pathogens which is an alternative to the classical way of identifying immunogenic proteins is not well-known. In recent years several new applications for oligopeptide phage display in disease related fields have been developed which has led to the identification of various new antigens. These novel identified immunogenic proteins provide new insights into host pathogen interactions and can be used for the development of new diagnostic tests and vaccines. In this review we focus on the M13 oligopeptide phage display system for pathogen research but will also give examples for lambda phage display and for applications in other disease related fields. In addition, a detailed technical work flow for the identification of immunogenic oligopeptides using the pHORF system is given. The described identification of immunogenic proteins of pathogens using oligopeptide phage display can be linked to antibody phage display resulting in a vaccine pipeline.
Topics: Antigens; Bacteriophage M13; Bacteriophage lambda; Cell Surface Display Techniques; Oligopeptides
PubMed: 24136040
DOI: 10.3390/v5102531 -
The oligopeptide transporters: a small gene family with a diverse group of substrates and functions?Molecular Plant May 2011Genes in the Oligopeptide Transport family encode integral membrane proteins that are believed to translocate their substrates from either the extracellular environment... (Review)
Review
Genes in the Oligopeptide Transport family encode integral membrane proteins that are believed to translocate their substrates from either the extracellular environment or an organelle into the cytosol. Phylogenetic analyses of plant transporters have revealed two distant clades: the Yellow Stripe-Like (YSL) proteins and the so-called Oligopeptide Transporters (OPTs), for which the family was named. Three categories of substrates have been identified for this family: small peptides, secondary amino acids bound to metals, and glutathione. Notably, the YSL transporters are involved in metal homeostasis through the translocation of metal-chelates, indicating a level of conservation both in biological function as well as substrates. In contrast, the functions of OPT proteins seem to be less defined and, in this review, I will examine the supporting and contradictory evidence for the proposed roles of OPTs in such diverse functions as long-distance sulfur distribution, nitrogen mobilization, metal homeostasis, and heavy metal sequestration through the transport of glutathione, metal-chelates, and peptides.
Topics: Membrane Transport Proteins; Metals; Multigene Family; Oligopeptides; Plants; Substrate Specificity
PubMed: 21310763
DOI: 10.1093/mp/ssr004 -
Biochemical Society Transactions Apr 2020Solute carrier (SLC) transporters play important roles in regulating the movement of small molecules and ions across cellular membranes. In mammals, they play an... (Review)
Review
Solute carrier (SLC) transporters play important roles in regulating the movement of small molecules and ions across cellular membranes. In mammals, they play an important role in regulating the uptake of nutrients and vitamins from the diet, and in controlling the distribution of their metabolic intermediates within the cell. Several SLC families also play an important role in drug transport and strategies are being developed to hijack SLC transporters to control and regulate drug transport within the body. Through the addition of amino acid and peptide moieties several novel antiviral and anticancer agents have been developed that hijack the proton-coupled oligopeptide transporters, PepT1 (SCL15A1) and PepT2 (SLC15A2), for improved intestinal absorption and renal retention in the body. A major goal is to understand the rationale behind these successes and expand the library of prodrug molecules that utilise SLC transporters. Recent co-crystal structures of prokaryotic homologues of the human PepT1 and PepT2 transporters have shed important new insights into the mechanism of prodrug recognition. Here, I will review recent developments in our understanding of ligand recognition and binding promiscuity within the SLC15 family, and discuss current models for prodrug recognition.
Topics: Animals; Biological Transport; Crystallography, X-Ray; Drug Design; Humans; Oligopeptides; Peptide Transporter 1; Prodrugs; Symporters; Valacyclovir; Valganciclovir
PubMed: 32219385
DOI: 10.1042/BST20180302 -
Biomolecules Nov 2019Short oligopeptides are some of the most promising and functionally important amide bond-containing components, with widespread applications. Biosynthesis of these... (Review)
Review
Short oligopeptides are some of the most promising and functionally important amide bond-containing components, with widespread applications. Biosynthesis of these oligopeptides may potentially become the ultimate strategy because it has better cost efficiency and environmental-friendliness than conventional solid phase peptide synthesis and chemo-enzymatic synthesis. To successfully apply this strategy for the biosynthesis of structurally diverse amide bond-containing components, the identification and selection of specific biocatalysts is extremely important. Given that perspective, this review focuses on the current knowledge about the typical enzymes that might be potentially used for the synthesis of short oligopeptides. Moreover, novel enzymatic methods of producing desired peptides via metabolic engineering are highlighted. It is believed that this review will be helpful for technological innovation in the production of desired peptides.
Topics: Green Chemistry Technology; Oligopeptides
PubMed: 31766233
DOI: 10.3390/biom9110733 -
Biomolecules May 2022Flory's random coil model assumes that conformational fluctuations of amino acid residues in unfolded poly(oligo)peptides and proteins are uncorrelated (isolated pair...
Flory's random coil model assumes that conformational fluctuations of amino acid residues in unfolded poly(oligo)peptides and proteins are uncorrelated (isolated pair hypothesis, IPH). This implies that conformational energies, entropies and solvation free energies are all additive. Nearly 25 years ago, analyses of coil libraries cast some doubt on this notion, in that they revealed that aromatic, but also β-branched side chains, could change the J(HH) coupling of their neighbors. Since then, multiple bioinformatical, computational and experimental studies have revealed that conformational propensities of amino acids in unfolded peptides and proteins depend on their nearest neighbors. We used recently reported and newly obtained Ramachandran plots of tetra- and pentapeptides with non-terminal homo- and heterosequences of amino acid residues to quantitatively determine nearest neighbor coupling between them with a Ising type model. Results reveal that, depending on the choice of amino acid residue pairs, nearest neighbor interactions either stabilize or destabilize pairs of polyproline II and β-strand conformations. This leads to a redistribution of population between these conformations and a reduction in conformational entropy. Interactions between residues in polyproline II and turn(helix)-forming conformations seem to be cooperative in most cases, but the respective interaction parameters are subject to large statistical errors.
Topics: Amino Acids; Molecular Conformation; Oligopeptides; Peptides; Proteins
PubMed: 35625612
DOI: 10.3390/biom12050684 -
Blood Oct 2008A growing body of evidence suggests that peptides containing the Asn-Gly-Arg (NGR) motif can selectively recognize tumor neovasculature and can be used, therefore, for... (Review)
Review
A growing body of evidence suggests that peptides containing the Asn-Gly-Arg (NGR) motif can selectively recognize tumor neovasculature and can be used, therefore, for ligand-directed targeted delivery of various drugs and particles to tumors or to other tissues with an angiogenesis component. The neovasculature binding properties of these peptides rely on the interaction with an endothelium-associated form of aminopeptidase N (CD13), an enzyme that has been implicated in angiogenesis and tumor growth. Recent studies have shown that NGR can rapidly convert to isoaspartate-glycine-arginine (isoDGR) by asparagine deamidation, generating alpha(v)beta(3) ligands capable of affecting endothelial cell functions and tumor growth. This review focuses on structural and functional properties of the NGR motif and its application in drug development for angiogenesis-dependent diseases. Furthermore, we discuss the time-dependent transition of NGR to isoDGR in natural proteins, such as fibronectins, and its potential role of as a "molecular timer" for generating new binding sites for integrins impli-cated in angiogenesis.
Topics: Amino Acid Motifs; Animals; Cell Adhesion; Drug Delivery Systems; Humans; Integrins; Neovascularization, Pathologic; Oligopeptides
PubMed: 18574027
DOI: 10.1182/blood-2008-04-150862 -
International Journal of Molecular... Feb 2023In this project, we combine two areas of research, experimental characterization and molecular docking studies of the interaction of positively charged oligopeptides...
In this project, we combine two areas of research, experimental characterization and molecular docking studies of the interaction of positively charged oligopeptides with crucial blood plasma proteins. The investigated peptides are rich in NH groups of amino acid side chains from Dap, Orn, Lys, and Arg residues, which are relevant in protein interaction. The peptides are 9- and 11-mer with the following sequences: (Lys-Dab-Dab-Gly-Orn-Pro-His-Lys-Arg-Lys-Dbt), (Lys-Dab-Ala-Gly-Orn-Pro-His-Lys-Arg), and (Lys-Dab-Dab-Gly-Orn-Pro-Phe(2-F)-Lys-Arg). The net charge of the compound strongly depends on the pH environment and it is an important aspect of protein binding. The studied oligopeptides exhibit therapeutic properties: anti-inflammatory activity and the capacity to diminish reactive oxygen species (ROS). Therefore, the mechanism of potential binding with blood plasma components is the next challenge. The binding interaction has been investigated under pseudo-physiological conditions with the main blood plasma proteins: albumin (BSA), α1-acid glycoprotein (AAG), and γ-globulin fraction (GGF). The biomolecular quenching constant (k) and binding constant (K) were obtained by fluorescence spectroscopy at various temperatures. Simultaneously, the changes in the secondary structure of proteins were monitored by circular dichroism (CD) and infrared spectroscopy (IR) by quantity analysis. Moreover, molecular docking studies were conducted to estimate the binding affinity, the binding domain, and the chemical nature of these interactions. The results show that the investigated oligopeptides could be mainly transported by albumin, and the binding domain I is the most favored cavity. The BSA and GGF are able to form stable complexes with the studied compounds as opposed to AAG. The binding reactions are spontaneous processes. The highest binding constants were determined for Lys-Dab-Dab-Gly-Orn-Pro-His-Lys-Arg-Lys-Dbt peptide, in which the values of the binding constants K to BSA and GGF were 10.1 × 10 dmmol and 3.39 × 10 dmmol, respectively. The positively charged surface of peptides participated in salt bridge interaction with proteins; however, hydrogen bonds were also formed. The secondary structure of BSA and GGF after contact with peptides was changed. A reduction in the α-helix structure was observed with an increase in the β-sheet and β-turn and random coil structures.
Topics: Amino Acid Sequence; Molecular Docking Simulation; Peptides; Oligopeptides; Lysine; Blood Proteins; Albumins
PubMed: 36769160
DOI: 10.3390/ijms24032836 -
Proceedings of the National Academy of... Nov 2001The spatial display of cellular ligands and receptors is important for cell adhesion and communication. Two approaches that emphasize developing selective methods to...
The spatial display of cellular ligands and receptors is important for cell adhesion and communication. Two approaches that emphasize developing selective methods to dissect, modify, and control receptor-ligand interactions at the cellular interface are discussed.
Topics: Amino Acid Sequence; Cell Adhesion; Cell Communication; Extracellular Matrix; Models, Molecular; Oligopeptides; Surface Properties
PubMed: 11687628
DOI: 10.1073/pnas.231391398 -
Scientific Reports Mar 2017Nucleic acid aptamers possess attractive features such as specific molecular recognition, high-affinity binding, and rapid acquisition and replication, which could be...
Nucleic acid aptamers possess attractive features such as specific molecular recognition, high-affinity binding, and rapid acquisition and replication, which could be feasible components for separating specific cells from other cell types. This study demonstrates that aptamers conjugated to an oligopeptide self-assembled monolayer (SAM) can be used to selectively trap human hepatic cancer cells from cell mixtures containing normal human hepatocytes or human fibroblasts. Molecular dynamics calculations have been performed to understand how the configurations of the aptamers are related to the experimental results of selective cell capture. We further demonstrate that the captured hepatic cancer cells can be detached and collected along with electrochemical desorption of the oligopeptide SAM, and by repeating these catch-and-release processes, target cells can be enriched. This combination of capture with aptamers and detachment with electrochemical reactions is a promising tool in various research fields ranging from basic cancer research to tissue engineering applications.
Topics: Aptamers, Nucleotide; Cell Line, Tumor; Cell Separation; Electrochemical Techniques; Humans; Oligopeptides
PubMed: 28266533
DOI: 10.1038/srep43375 -
Biomacromolecules Apr 2023End-capped peptides modified with reactive functional groups on the N-terminus provide a route to prepare peptide-polymer conjugates for a broad range of applications....
End-capped peptides modified with reactive functional groups on the N-terminus provide a route to prepare peptide-polymer conjugates for a broad range of applications. Unfortunately, current chemical methods to construct modified peptides rely largely on solid-phase peptide synthesis (SPPS), which lacks green preparative characteristics and is costly, thus limiting its applicability to specialty applications such as regenerative medicine. This work evaluates N-terminally modified -acryloyl-glutamic acid diethyl ester, -acryloyl-leucine ethyl ester, and -acryloyl-alanine ethyl ester as grafters and papain as the protease for the direct addition of amino acid ethyl ester (AA-OEt) monomers via protease-catalyzed peptide synthesis (PCPS) and the corresponding formation of -acryloyl-functionalized oligopeptides in a one-pot aqueous reaction. It was hypothesized that by building -acryloyl grafters from AA-OEt monomers that are known to be good substrates for papain in PCPS, the corresponding grafters would yield high grafter conversions, high ratio of grafter-oligopeptide to free NH-oligopeptide, and high overall yield. However, this work demonstrates based on the grafter/monomers studied herein that the dominant factor in -acryloyl-AA-OEt grafter conversion is the co-monomer used in co-oligomerizations. Computational modeling using Rosetta qualitatively recapitulates the results and provides insight into the structural and energetic bases underlying substrate selectivity. The findings herein expand our knowledge of factors that determine the efficiency of preparing -acryloyl-terminated oligopeptides by PCPS that could provide practical routes to peptide macromers for conjugation to polymers and surfaces for a broad range of applications.
Topics: Amino Acids; Peptide Hydrolases; Papain; Peptides; Oligopeptides; Polymers; Catalysis; Esters
PubMed: 36996092
DOI: 10.1021/acs.biomac.3c00029