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Nucleic Acids Research Jan 2016The BDB database (http://immunet.cn/bdb) is an update of the MimoDB database, which was previously described in the 2012 Nucleic Acids Research Database issue. The...
The BDB database (http://immunet.cn/bdb) is an update of the MimoDB database, which was previously described in the 2012 Nucleic Acids Research Database issue. The rebranded name BDB is short for Biopanning Data Bank, which aims to be a portal for biopanning results of the combinatorial peptide library. Last updated in July 2015, BDB contains 2904 sets of biopanning data collected from 1322 peer-reviewed papers. It contains 25,786 peptide sequences, 1704 targets, 492 known templates, 447 peptide libraries and 310 crystal structures of target-template or target-peptide complexes. All data stored in BDB were revisited, and information on peptide affinity, measurement method and procedures was added for 2298 peptides from 411 sets of biopanning data from 246 published papers. In addition, a more professional and user-friendly web interface was implemented, a more detailed help system was designed, and a new on-the-fly data visualization tool and a series of tools for data analysis were integrated. With these new data and tools made available, we expect that the BDB database would become a major resource for scholars using phage display, with improved utility for biopanning and related scientific communities.
Topics: Cell Surface Display Techniques; Databases, Chemical; Internet; Peptide Library; Peptides; Software
PubMed: 26503249
DOI: 10.1093/nar/gkv1100 -
Computational and Mathematical Methods... 2013
Topics: Bacteriophages; Computational Biology; Drug Delivery Systems; Epitope Mapping; Epitopes; Humans; Models, Theoretical; Peptide Library; Peptides; Protein Interaction Mapping; Software
PubMed: 24454540
DOI: 10.1155/2013/698395 -
Current Opinion in Biotechnology Aug 1997Peptidomimetics are one set of probes used in the transition pathway of small molecule drug design. Cyclization of the peptide backbone and its modification with... (Review)
Review
Peptidomimetics are one set of probes used in the transition pathway of small molecule drug design. Cyclization of the peptide backbone and its modification with aromatic residues constitutes an effective approach to mimetic drug design and circumvents obstacles associated with delivery and formulation of peptides and peptidomimetics. In the past year, examples of mimicking beta-turn structures has led to combining design strategies with molecular libraries, demonstrating that peptidomimetics can provide valuable clues about receptor similarities not revealed by their endogenous ligands. This information can lead to the development of dual inhibitors. In addition, this work suggests that the use of libraries and rational design need not be mutually exclusive approaches to lead discovery.
Topics: Animals; Drug Design; Humans; Ligands; Peptide Library; Peptides; Protein Engineering; Protein Structure, Secondary
PubMed: 9265722
DOI: 10.1016/s0958-1669(97)80065-1 -
Small Peptides in the Detection of Mycotoxins and Their Potential Applications in Mycotoxin Removal.Toxins Nov 2022Mycotoxins pose significant risks to humans and livestock. In addition, contaminated food- and feedstuffs can only be discarded, leading to increased economic losses and... (Review)
Review
Mycotoxins pose significant risks to humans and livestock. In addition, contaminated food- and feedstuffs can only be discarded, leading to increased economic losses and potential ecological pollution. Mycotoxin removal and real-time toxin level monitoring are effective approaches to solve this problem. As a hot research hotspot, small peptides derived from phage display peptide libraries, combinatorial peptide libraries, and rational design approaches can act as coating antigens, competitive antigens, and anti-immune complexes in immunoassays for the detection of mycotoxins. Furthermore, as a potential approach to mycotoxin degradation, small peptides can mimic the natural enzyme catalytic site to construct artificial enzymes containing oxidoreductases, hydrolase, and lyase activities. In summary, with the advantages of mature synthesis protocols, diverse structures, and excellent biocompatibility, also sharing their chemical structure with natural proteins, small peptides are widely used for mycotoxin detection and artificial enzyme construction, which have promising applications in mycotoxin degradation. This paper mainly reviews the advances of small peptides in the detection of mycotoxins, the construction of peptide-based artificial enzymes, and their potential applications in mycotoxin control.
Topics: Immunoassay; Mycotoxins; Peptide Library; Peptides
PubMed: 36422969
DOI: 10.3390/toxins14110795 -
BMB Reports Sep 2015The in vitro antibody discovery technologies revolutionized the generation of target-specific antibodies that traditionally relied on the humoral response of immunized... (Review)
Review
The in vitro antibody discovery technologies revolutionized the generation of target-specific antibodies that traditionally relied on the humoral response of immunized animals. An antibody library, a large collection of diverse, pre-constructed antibodies, can be rapidly screened using in vitro display technologies such as phage display. One of the keys to successful in vitro antibody discovery is the quality of the library diversity. Antibody diversity can be obtained either from natural B-cell sources or by the synthetic methods that combinatorially generate random nucleotide sequences. While the functionality of a natural antibody library depends largely upon the library size, various other factors can affect the quality of a synthetic antibody library, making the design and construction of synthetic antibody libraries complicated and challenging. In this review, we present various library designs and diversification methods for synthetic antibody library. From simple degenerate oligonucleotide synthesis to trinucleotide synthesis to physicochemically optimized library design, the synthetic approach is evolving beyond the simple emulation of natural antibodies, into a highly sophisticated method that is capable of producing high quality antibodies suitable for therapeutic, diagnostic, and other demanding applications. [BMB Reports 2015; 48(9): 489-494].
Topics: Animals; Antibodies; Antibody Diversity; Peptide Library; Synthetic Biology
PubMed: 26129672
DOI: 10.5483/bmbrep.2015.48.9.120 -
Viruses Apr 2024Phage display is a versatile method often used in the discovery of peptides that targets disease-related biomarkers. A major advantage of this technology is the ease and... (Review)
Review
Phage display is a versatile method often used in the discovery of peptides that targets disease-related biomarkers. A major advantage of this technology is the ease and cost efficiency of affinity selection, also known as biopanning, to identify novel peptides. While it is relatively straightforward to identify peptides with optimal binding affinity, the pharmacokinetics of the selected peptides often prove to be suboptimal. Therefore, careful consideration of the experimental conditions, including the choice of using in vitro, in situ, or in vivo affinity selections, is essential in generating peptides with high affinity and specificity that also demonstrate desirable pharmacokinetics. Specifically, in vivo biopanning, or the combination of in vitro, in situ, and in vivo affinity selections, has been proven to influence the biodistribution and clearance of peptides and peptide-conjugated nanoparticles. Additionally, the marked difference in properties between peptides and nanoparticles must be considered. While peptide biodistribution depends primarily on physiochemical properties and can be modified by amino acid modifications, the size and shape of nanoparticles also affect both absorption and distribution. Thus, optimization of the desired pharmacokinetic properties should be an important consideration in biopanning strategies to enable the selection of peptides and peptide-conjugated nanoparticles that effectively target biomarkers in vivo.
Topics: Peptides; Animals; Cell Surface Display Techniques; Humans; Tissue Distribution; Nanoparticles; Peptide Library
PubMed: 38675913
DOI: 10.3390/v16040570 -
Nature Methods Sep 2017Data-independent acquisition (DIA) is an emerging mass spectrometry (MS)-based technique for unbiased and reproducible measurement of protein mixtures. DIA tandem mass...
Data-independent acquisition (DIA) is an emerging mass spectrometry (MS)-based technique for unbiased and reproducible measurement of protein mixtures. DIA tandem mass spectrometry spectra are often highly multiplexed, containing product ions from multiple cofragmenting precursors. Detecting peptides directly from DIA data is therefore challenging; most DIA data analyses require spectral libraries. Here we present PECAN (http://pecan.maccosslab.org), a library-free, peptide-centric tool that robustly and accurately detects peptides directly from DIA data. PECAN reports evidence of detection based on product ion scoring, which enables detection of low-abundance analytes with poor precursor ion signal. We demonstrate the chromatographic peak picking accuracy and peptide detection capability of PECAN, and we further validate its detection with data-dependent acquisition and targeted analyses. Lastly, we used PECAN to build a plasma proteome library from DIA data and to query known sequence variants.
Topics: Algorithms; Gene Expression Profiling; Peptide Library; Proteome; Reproducibility of Results; Sensitivity and Specificity; Software; Tandem Mass Spectrometry
PubMed: 28783153
DOI: 10.1038/nmeth.4390 -
Chembiochem : a European Journal of... Jun 2022DNA-encoded small-molecule libraries and mRNA displayed peptide libraries both use numerically large pools of oligonucleotide-tagged molecules to identify potential hits... (Review)
Review
DNA-encoded small-molecule libraries and mRNA displayed peptide libraries both use numerically large pools of oligonucleotide-tagged molecules to identify potential hits for protein targets. They differ dramatically, however, in the 'drug-likeness' of the molecules that each can be used to discover. We give here an overview of the two techniques, comparing some advantages and disadvantages of each, and suggest areas where particularly mRNA display can benefit from adopting advances developed with DNA-encoded small molecule libraries. We outline cases where chemical modification of the peptide library has already been used in mRNA display, and survey opportunities to expand this using examples from DNA-encoded small molecule libraries. We also propose potential opportunities for encoding such reactions within the mRNA/cDNA tag of an mRNA-displayed peptide library to allow a more diversity-oriented approach to library modification. Finally, we outline alternate approaches for enriching target-binding hits from a pooled and tagged library, and close by detailing several examples of how an adjusted mRNA-display based approach could be used to discover new 'drug-like' modified small peptides.
Topics: DNA; Drug Discovery; Peptide Library; RNA, Messenger; Small Molecule Libraries
PubMed: 35100479
DOI: 10.1002/cbic.202100685 -
Journal of Proteome Research Jun 2022Advances in library-based methods for peptide detection from data-independent acquisition (DIA) mass spectrometry have made it possible to detect and quantify tens of...
Advances in library-based methods for peptide detection from data-independent acquisition (DIA) mass spectrometry have made it possible to detect and quantify tens of thousands of peptides in a single mass spectrometry run. However, many of these methods rely on a comprehensive, high-quality spectral library containing information about the expected retention time and fragmentation patterns of peptides in the sample. Empirical spectral libraries are often generated through data-dependent acquisition and may suffer from biases as a result. Spectral libraries can be generated in silico, but these models are not trained to handle all possible post-translational modifications. Here, we propose a false discovery rate-controlled spectrum-centric search workflow to generate spectral libraries directly from gas-phase fractionated DIA tandem mass spectrometry data. We demonstrate that this strategy is able to detect phosphorylated peptides and can be used to generate a spectral library for accurate peptide detection and quantitation in wide-window DIA data. We compare the results of this search workflow to other library-free approaches and demonstrate that our search is competitive in terms of accuracy and sensitivity. These results demonstrate that the proposed workflow has the capacity to generate spectral libraries while avoiding the limitations of other methods.
Topics: Peptide Library; Peptides; Protein Processing, Post-Translational; Proteome; Tandem Mass Spectrometry; Workflow
PubMed: 35549345
DOI: 10.1021/acs.jproteome.1c00895 -
Journal of the American Chemical Society Nov 2022Efficient, site-specific, and bio-orthogonal conjugation of chemical functionalities to proteins is of great utility in fundamental research as well as industrial...
Efficient, site-specific, and bio-orthogonal conjugation of chemical functionalities to proteins is of great utility in fundamental research as well as industrial processes (e.g., the production of antibody-drug conjugates and immobilization of enzymes for biocatalysis). A popular approach involves reacting a free N-terminal cysteine with a variety of electrophilic reagents. However, current methods for generating proteins with N-terminal cysteines have significant limitations. Herein we report a novel, efficient, and convenient method for producing recombinant proteins with free N-terminal cysteines by genetically fusing a Met-Pro-Cys sequence to the N-terminus of a protein of interest and subjecting the recombinant protein to the sequential action of methionine and proline aminopeptidases. The resulting protein was site-specifically labeled at the N-terminus with fluorescein and a cyclic cell-penetrating peptide through native chemical ligation and a 2-cyanobenzothiazole moiety, respectively. In addition, the optimal recognition sequence of proline aminopeptidase was determined by screening a combinatorial peptide library and incorporated into the N-terminus of a protein of interest for most efficient N-terminal processing.
Topics: Cysteine; Aminopeptidases; Recombinant Proteins; Fluorescein; Peptide Library
PubMed: 36378906
DOI: 10.1021/jacs.2c10194