Mimotope

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A mimotope is often a peptide, and mimics the structure of an epitope. Because of this property it causes an antibody response similar to the one elicited by the epitope. An antibody for a given epitope antigen will recognize a mimotope which mimics that epitope. Mimotopes are commonly obtained from phage display libraries through biopanning. Vaccines utilizing mimotopes are being developed. Mimotopes are a kind of peptide aptamers.

When the term mimotope was first coined by Mario Geysen in 1986, [1] it was used to describe peptides mimicking epitopes. However, this concept has been extended to refer peptide mimic of all types of binding sites. As the mimic of binding site, mimotope analysis has been widely used in mapping epitopes, [2] identifying drug target and inferring protein interaction networks. [3] [4] Furthermore, mimotope has also shown its potential in the development of new diagnostics, [5] therapeutics [6] and vaccines. [7] In addition, special affinities mediated by mimotopes to various semiconductors and other materials have shown very encouraging promise in new material and new energy studies. [8] Gathering information on mimotopes into a special database therefore deserves. In 2010, the MimoDB database version 1.0 was released. [9] It had 10716 peptides grouped into 1229 sets. These peptides were extracted from biopanning results of phage-displayed random peptide libraries reported in 571 papers. The MimoDB database has been updated to the current version 2.0 very recently. [10] In version 2.0, it has 15633 peptides collected from 849 papers and grouped into 1818 sets. Besides the core data on panning experiments and their results, broad background information on target, template, library and structure is included. An accompanied benchmark has also been compiled for bioinformaticians to develop and evaluate their new models, algorithms and programs. In addition, the MimoDB database provides tools for simple and advanced searches, structure visualization, BLAST and alignment view on the fly. The experimental biologists can easily use the database as a virtual control to exclude possible target-unrelated peptides. The MimoDB database [11] is freely available.

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<span class="mw-page-title-main">Antigen</span> Molecule triggering an immune response (antibody production) in the host

In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.

<span class="mw-page-title-main">Antibody</span> Protein(s) forming a major part of an organisms immune system

An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the pathogen, called an antigen. Each tip of the "Y" of an antibody contains a paratope that is specific for one particular epitope on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can tag a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly.

<span class="mw-page-title-main">Major histocompatibility complex</span> Cell surface proteins, part of the acquired immune system

The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are called MHC molecules.

<span class="mw-page-title-main">Monoclonal antibody</span> Antibodies from clones of the same blood cell

A monoclonal antibody is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell.

An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that binds to the epitope is called a paratope. Although epitopes are usually non-self proteins, sequences derived from the host that can be recognized are also epitopes.

<span class="mw-page-title-main">Peptidomimetic</span> Class of compounds designed to mimic features of peptides

A peptidomimetic is a small protein-like chain designed to mimic a peptide. They typically arise either from modification of an existing peptide, or by designing similar systems that mimic peptides, such as peptoids and β-peptides. Irrespective of the approach, the altered chemical structure is designed to advantageously adjust the molecular properties such as stability or biological activity. This can have a role in the development of drug-like compounds from existing peptides. Peptidomimetics can be prepared by cyclization of linear peptides or coupling of stable unnatural amino acids. These modifications involve changes to the peptide that will not occur naturally. Unnatural amino acids can be generated from their native analogs via modifications such as amine alkylation, side chain substitution, structural bond extension cyclization, and isosteric replacements within the amino acid backbone. Based on their similarity with the precursor peptide, peptidomimetics can be grouped into four classes where A features the most and D the least similarities. Classes A and B involve peptide-like scaffolds, while classes C and D include small molecules.

<span class="mw-page-title-main">Phage display</span> Biological technique to evolve proteins using bacteriophages

Phage display is a laboratory technique for the study of protein–protein, protein–peptide, and protein–DNA interactions that uses bacteriophages to connect proteins with the genetic information that encodes them. In this technique, a gene encoding a protein of interest is inserted into a phage coat protein gene, causing the phage to "display" the protein on its outside while containing the gene for the protein on its inside, resulting in a connection between genotype and phenotype. The proteins that the phages are displaying can then be screened against other proteins, peptides or DNA sequences, in order to detect interaction between the displayed protein and those of other molecules. In this way, large libraries of proteins can be screened and amplified in a process called in vitro selection, which is analogous to natural selection.

<span class="mw-page-title-main">Aptamer</span> Oligonucleotide or peptide molecules that bind specific targets

Aptamers are short sequences of artificial DNA, RNA, XNA, or peptide that bind a specific target molecule, or family of target molecules. They exhibit a range of affinities, with variable levels of off-target binding and are sometimes classified as chemical antibodies. Aptamers and antibodies can be used in many of the same applications, but the nucleic acid-based structure of aptamers, which are mostly oligonucleotides, is very different from the amino acid-based structure of antibodies, which are proteins. This difference can make aptamers a better choice than antibodies for some purposes.

<span class="mw-page-title-main">Epitope mapping</span> Identifying the binding site of an antibody on its target antigen

In immunology, epitope mapping is the process of experimentally identifying the binding site, or epitope, of an antibody on its target antigen. Identification and characterization of antibody binding sites aid in the discovery and development of new therapeutics, vaccines, and diagnostics. Epitope characterization can also help elucidate the binding mechanism of an antibody and can strengthen intellectual property (patent) protection. Experimental epitope mapping data can be incorporated into robust algorithms to facilitate in silico prediction of B-cell epitopes based on sequence and/or structural data.

<span class="mw-page-title-main">Single-domain antibody</span> Antibody fragment

A single-domain antibody (sdAb), also known as a Nanobody, is an antibody fragment consisting of a single monomeric variable antibody domain. Like a whole antibody, it is able to bind selectively to a specific antigen. With a molecular weight of only 12–15 kDa, single-domain antibodies are much smaller than common antibodies which are composed of two heavy protein chains and two light chains, and even smaller than Fab fragments and single-chain variable fragments.

In academia, computational immunology is a field of science that encompasses high-throughput genomic and bioinformatics approaches to immunology. The field's main aim is to convert immunological data into computational problems, solve these problems using mathematical and computational approaches and then convert these results into immunologically meaningful interpretations.

Bacterial display is a protein engineering technique used for in vitro protein evolution. Libraries of polypeptides displayed on the surface of bacteria can be screened using flow cytometry or iterative selection procedures (biopanning). This protein engineering technique allows us to link the function of a protein with the gene that encodes it. Bacterial display can be used to find target proteins with desired properties and can be used to make affinity ligands which are cell-specific. This system can be used in many applications including the creation of novel vaccines, the identification of enzyme substrates and finding the affinity of a ligand for its target protein.

Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted:

Molecular mimicry is the theoretical possibility that sequence similarities between foreign and self-peptides are enough to result in the cross-activation of autoreactive T or B cells by pathogen-derived peptides. Despite the prevalence of several peptide sequences which can be both foreign and self in nature, just a few crucial residues can activate a single antibody or TCR. This highlights the importance of structural homology in the theory of molecular mimicry. Upon activation, these "peptide mimic" specific T or B cells can cross-react with self-epitopes, thus leading to tissue pathology (autoimmunity). Molecular mimicry is one of several ways in which autoimmunity can be evoked. A molecular mimicking event is more than an epiphenomenon despite its low probability, and these events have serious implications in the onset of many human autoimmune disorders.

Biopanning is an affinity selection technique which selects for peptides that bind to a given target. All peptide sequences obtained from biopanning using combinatorial peptide libraries have been stored in a special freely available database named BDB. This technique is often used for the selection of antibodies too.

Computational Resources for Drug Discovery (CRDD) is one of the important silico modules of Open Source for Drug Discovery (OSDD). The CRDD web portal provides computer resources related to drug discovery on a single platform. It provides computational resources for researchers in computer-aided drug design, a discussion forum, and resources to maintain a wiki related to drug discovery, predict inhibitors, and predict the ADME-Tox property of molecules. One of the major objectives of CRDD is to promote open source software in the field of chemoinformatics and pharmacoinformatics.

Avimers are artificial proteins that are able to specifically bind to certain antigens via multiple binding sites. Since they are not structurally related to antibodies, they are classified as a type of antibody mimetic. Avimers have been developed by the biotechnology company Avidia, now part of Amgen, as potential new pharmaceutical drugs.

Peptide-based synthetic vaccines are subunit vaccines made from peptides. The peptides mimic the epitopes of the antigen that triggers direct or potent immune responses. Peptide vaccines can not only induce protection against infectious pathogens and non-infectious diseases but also be utilized as therapeutic cancer vaccines, where peptides from tumor-associated antigens are used to induce an effective anti-tumor T-cell response.

<span class="mw-page-title-main">Peptide microarray</span>

A peptide microarray is a collection of peptides displayed on a solid surface, usually a glass or plastic chip. Peptide chips are used by scientists in biology, medicine and pharmacology to study binding properties and functionality and kinetics of protein-protein interactions in general. In basic research, peptide microarrays are often used to profile an enzyme, to map an antibody epitope or to find key residues for protein binding. Practical applications are seromarker discovery, profiling of changing humoral immune responses of individual patients during disease progression, monitoring of therapeutic interventions, patient stratification and development of diagnostic tools and vaccines.

James Allen Wells is a Professor of Pharmaceutical Chemistry and Cellular & Molecular Pharmacology at the University of California, San Francisco (UCSF) and a member of the National Academy of Sciences. He received his B.A. degrees in biochemistry and psychology from University of California, Berkeley in 1973 and a PhD in biochemistry from Washington State University with Ralph Yount, PhD in 1979. He completed his postdoctoral studies at Stanford University School of Medicine with George Stark in 1982. He is a pioneer in protein engineering, phage display, fragment-based lead discovery, cellular apoptosis, and the cell surface proteome.

References

  1. ↑ Geysen, HM; Rodda, SJ; Mason, TJ (July 1986). "A priori delineation of a peptide which mimics a discontinuous antigenic determinant". Molecular Immunology. 23 (7): 709–15. doi:10.1016/0161-5890(86)90081-7. PMID   2432410.
  2. ↑ Smith, GP; Petrenko, VA (1997-04-01). "Phage Display". Chemical Reviews. 97 (2): 391–410. doi:10.1021/cr960065d. PMID   11848876.
  3. ↑ Tong, AH; Drees, B; Nardelli, G; Bader, GD; Brannetti, B; Castagnoli, L; Evangelista, M; Ferracuti, S; Nelson, B; Paoluzi, S; Quondam, M; Zucconi, A; Hogue, CW; Fields, S; Boone, C; Cesareni, G (2002-01-11). "A combined experimental and computational strategy to define protein interaction networks for peptide recognition modules". Science. 295 (5553): 321–4. doi: 10.1126/science.1064987 . PMID   11743162. S2CID   17604414.
  4. ↑ Thom, G; Cockroft, AC; Buchanan, AG; Candotti, CJ; Cohen, ES; Lowne, D; Monk, P; Shorrock-Hart, CP; Jermutus, L; Minter, RR (2006-05-16). "Probing a protein-protein interaction by in vitro evolution". Proceedings of the National Academy of Sciences of the United States of America. 103 (20): 7619–24. Bibcode:2006PNAS..103.7619T. doi: 10.1073/pnas.0602341103 . PMC   1458619 . PMID   16684878.
  5. ↑ Hsiung, PL; Hardy, J; Friedland, S; Soetikno, R; Du, CB; Wu, AP; Sahbaie, P; Crawford, JM; Lowe, AW; Contag, CH; Wang, TD (April 2008). "Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy". Nature Medicine. 14 (4): 454–8. doi:10.1038/nm1692. PMC   3324975 . PMID   18345013.
  6. ↑ Macdougall, IC; Rossert, J; Casadevall, N; Stead, RB; Duliege, AM; Froissart, M; Eckardt, KU (2009-11-05). "A peptide-based erythropoietin-receptor agonist for pure red-cell aplasia". The New England Journal of Medicine. 361 (19): 1848–55. doi: 10.1056/NEJMoa074037 . PMID   19890127.
  7. ↑ Knittelfelder, R; Riemer, AB; Jensen-Jarolim, E (April 2009). "Mimotope vaccination--from allergy to cancer". Expert Opinion on Biological Therapy. 9 (4): 493–506. doi:10.1517/14712590902870386. PMC   3049225 . PMID   19344285.
  8. ↑ Lee, YJ; Yi, H; Kim, WJ; Kang, K; Yun, DS; Strano, MS; Ceder, G; Belcher, AM (2009-05-22). "Fabricating genetically engineered high-power lithium-ion batteries using multiple virus genes". Science. 324 (5930): 1051–5. Bibcode:2009Sci...324.1051L. doi: 10.1126/science.1171541 . PMID   19342549. S2CID   32017913.
  9. ↑ Ru, B; Huang, J; Dai, P; Li, S; Xia, Z; Ding, H; Lin, H; Guo, F; Wang, X (2010-11-15). "MimoDB: a new repository for mimotope data derived from phage display technology". Molecules (Basel, Switzerland). 15 (11): 8279–88. doi: 10.3390/molecules15118279 . PMC   6259156 . PMID   21079566.
  10. ↑ Huang, J; Ru, B; Zhu, P; Nie, F; Yang, J; Wang, X; Dai, P; Lin, H; Guo, FB; Rao, N (2011-11-03). "MimoDB 2.0: a mimotope database and beyond". Nucleic Acids Research. 40 (1): D271–7. doi:10.1093/nar/gkr922. PMC   3245166 . PMID   22053087.
  11. ↑ "The MimoDB database". Archived from the original on 2012-11-16. Retrieved 2011-11-07.


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