![]() Another particularly illustrative example of the use of peptides in diagnostics is the highly sensitive and specific detection of anti-citrullinated protein Abs, associated with rheumatoid arthritis, using synthetic peptides containing citrulline, which in vivo arises by post-translational modification (PTM) of Arg. They successfully used a peptide representing a predicted immune-dominant (linear) epitope in Dengue Virus Envelope protein to detect Abs in infected individuals. One example of the use of synthetic peptides in diagnostics is the detection of Dengue virus Abs, as described by Bergamaschi et al. Since 2000, 28 new peptide drugs have been approved for a wide range of conditions, cancer, infections, metabolic diseases, haematology, cardiovascular diseases, and osteoporosis. Synthetic peptides are important therapeutics, and, in the last two decades, a significant renaissance in peptide drug discovery has occurred. Synthetic peptides have numerous applications in research, diagnostics, and treatment, epitope characterization, production of peptide Abs, and vaccine development ( Table 1). Following synthesis, the peptide is cleaved from the solid-support with acid.įrom here on, the maturation of the field was mainly driven by the introduction of analytical and preparative reversed-phase high-performance liquid chromatography and mass spectrometry (MS) techniques such as matrix-assisted linear desorption-ionisation Time-Of-Flight, MALDI TOF MS, and liquid chromatography, LC-MS, which made it possible for most laboratories to purify and characterize their peptide products. In SPPS, the peptide chain is elongated toward the N-terminus in a step-wise manner using a protecting group for the Nα-amino group and semi-permanent groups for side chains. Previously, peptides were synthesized in solution and purified after each coupling step. In 1963, Robert Bruce Merrifield introduced the solid-phase peptide synthesis (SPPS) principle, in which a growing peptide chain is linked through the C-terminal end to a solid-support. ( e) Neuropeptide Y, a 36-amino acid peptide hormone containing an α-helix. ( d) Oxytocin, a small disulfide bridge-constrained uterus-contracting nona-peptide hormone. ( c) Luteinizing hormone releasing hormone, a β-strand deca-peptide hormone. ( b) Met-enkephalin, a non-structured opioid penta-peptide. ( b– e) Examples of smaller bioactive peptide hormones also illustrating particular conformational aspects. The box indicates a peptide bond (-CO-NH-). ![]() ( a) Amino acid and peptide bond structure. Īmino acids, peptide bonds, polypeptides, and proteins. Protein sequencers with Edman degradation became available in the late 1960s, and ninhydrin-based amino acid analysis was introduced by Moore and Stein who elucidated the structure of ribonuclease A in 1973. Further advances in the field included Edman degradation and amino acid analysis with the former being a method for sequencing a peptide one N-terminal residue at a time. In 1953, Du Vigneaud and co-workers synthesized the first biologically active peptide, oxytocin, a uterus-contracting hormone containing nine amino acids and a disulfide bond, as shown in Figure 1 together with other examples of bioactive peptides. The field slowly developed by introducing protecting groups for the Nα-amino group and side-chain functional groups as well as more effective coupling reagents for peptide bond formation. The history of peptide chemistry dates back to around 1900, where Emil Fischer synthesized small peptides containing glycine residues. In addition, new molecule types are being developed to complement the use of the traditional reagents and these may become more useful if the technologies can be improved. This applies to research and diagnostics but also to therapy and may become relevant to prevention of disease (vaccination). Today, molecular biology still depends on the use of peptides, Abs, and peptide Abs. Peptides were also crucial reagents for elucidating the molecular biology of Ab specificity and biosynthesis, both with regard to B cell specificity and development and with regard to antigen presentation and T cell specificity and development. These advances led to the realization that Abs and a major group of Ags are themselves proteins. Peptide chemistry formed the basis of understanding protein composition and structure and Abs lay the foundation for molecular immunology, even though the relationship between Abs and antigens (Ags) had to await advances in peptide and protein chemistry. Peptides and antibodies (Abs) have entered a fruitful companionship in immunology since they were discovered.
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