Exploration of Drug Science

Algorithm	Web address
Antheprot [6]	https://www.gdeleage.fr/antheprot/
Immune epitope database (IEDB) [14]	http://tools.iedb.org/bcell/
ABCpred [15]	https://webs.iiitd.edu.in/raghava/abcpred/ABC_submission.html
BCPREDS [16]	http://ailab-projects2.ist.psu.edu/bcpred/predict.html
Immnunomedicine group [17]	http://imed.med.ucm.es/Tools/antigenic.pl
SVMTriP [18]	http://sysbio.unl.edu/SVMTriP/prediction.php

Declarations

Acknowledgments

We dedicate this publication to Dr. Manuel Elkin Patarroyo Murillo, who passed away on January 9th, 2025. He was a fundamental factor in the creation of our research group and supported training in the immunochemical area of the team, particularly in everything related to the chemical synthesis of peptides. He was also a great role model as a researcher who dedicated his life to generating well-being for the most vulnerable populations on the planet as a pioneer in the development of synthetic vaccines and the training of a very large group of scientists at the Colombian Institute of Immunology in Bogotá.

Author contributions

ON: Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Supervision, Validation, Visualization, Writing—original draft, Writing—review & editing. HB: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Resources, Validation, Visualization, Writing—original draft, Writing—review & editing. DP: Conceptualization, Formal analysis, Investigation, Methodology, Resources, Validation, Visualization, Writing—original draft, Writing—review & editing. BAdN: Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Validation, Visualization, Writing—original draft, Writing—review & editing. DOP: Data curation, Investigation, Methodology, Validation, Visualization, Writing—original draft, Writing—review & editing. FHP: Data curation, Funding acquisition, Investigation, Methodology, Project administration, Validation, Visualization, Writing—original draft, Writing—review & editing. SL: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Supervision, Validation, Visualization, Writing—original draft, Writing—review & editing. All authors have read and agreed to the published version of the manuscript.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This article summarizes the research produced in the area of synthetic peptides with diagnostic value for infectious diseases, generated by several research projects that were approved by different bioethics committees that comply with international regulations to respect ethical standards related to studies with human beings. Regarding the non-published results for patients with HIV/AIDS, the Bioethics Committee of the Instituto Venezolano de Investigaciones Científicas (IVIC) approved the use of sera from patients in the project titled: “Viral hepatitis and AIDS: molecular characteristics of infections in Venezuela (G-2005000394)” at Meeting No. 1323 on May 20th, 2009. Similarly, the sera of patients with Helicobacter pylori infection were used with the consent of the Ethical Committee of the Instituto de Biomedicina on November 14th, 2006, with the project titled: “Immunological profile, genotype and pathologies associated with Helicobacter pylori in Venezuelan individuals”. This study complies with the 2024 Declaration of Helsinki.

Consent to participate

Informed consent to participate in the study was obtained from all participants.

Consent to publication

Not applicable.

Availability of data and materials

The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.

Funding

Funding was obtained via the following grants: Corporación Andina de Fomento (CAF) 1992; National Laboratory of Proteomics and Immunochemistry of Proteins [FONACIT-2005]; Melinda & Bill Gates Foundation 2017 project No. [OPP1151004]; FONACIT 2022–2024 project No. [20220PGP129]; FONACIT 2022–2024 project No. [20220PGP130]; FONACIT 2024–2026 project CFP No. [2024000297]; FONACIT project PEI No. [20122000815]; FONACIT 2022 project No. [20220PGP06]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Goldsby RA, Kindt TJ, Osborne BA, Kuby J. Chapter 3. In: Immunology. 5th ed. New York: W. H. Freeman and Company; 2004. pp. 61–80.

Noya O, Alarcón de Noya B. The multiple antigen blot assay (MABA): a simple immunoenzymatic technique for simultaneous screening of multiple antigens. Immunol Lett. 1998;63:53–6. [DOI] [PubMed]

Noya O, Losada S, Toledo M, Gauna A, Lorenzo MA, Bermúdez H, et al. Improvements and Variants of the Multiple Antigen Blot Assay-MABA: An Immunoenzymatic Technique for Simultaneous Antigen and Antibody Screening. Methods Mol Biol. 2015;1312:301–19. [DOI] [PubMed]

Merrifield RB. Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide. J Am Chem Soc. 1963;85:2149–54. [DOI]

Houghten RA, DeGraw ST, Bray MK. Simultaneous multiple peptide synthesis: The rapid preparation of large numbers of discrete peptides for biological, immunological, and methodological studies. BioTechniques. 1986;4:522–8.

Deléage G, Combet C, Blanchet C, Geourjon C. ANTHEPROT: an integrated protein sequence analysis software with client/server capabilities. Comput Biol Med. 2001;31:259–67. [DOI] [PubMed]

Joshi S, Singh A, Saqib U, Misra P, Siddiqi M, Saxena J. Identification of potential P. falciparum transketolase inhibitors: pharmacophore design, in silico screening and docking studies. J Biophys Chem. 2010;1:96–104. [DOI]

Carpino LA, Hang GY. 9-Fluorenylmethoxycarbonyl amino-protecting group. J Org Chem. 1972;37:3404–9. [DOI]

Frank R. Spot-synthesis: an easy technique for the positionally addressable, parallel chemical synthesis on a membrane support. Tetrahedron. 1992;48:9217–32. [DOI]

10.

Hilpert K, Winkler DF, Hancock RE. Peptide arrays on cellulose support: SPOT synthesis, a time and cost efficient method for synthesis of large numbers of peptides in a parallel and addressable fashion. Nat Protoc. 2007;2:1333–49. [DOI] [PubMed]

11.

Engvall E, Perlmann P. Enzyme-linked immunosorbent assay (ELISA) quantitative assay of immunoglobulin G. Immunochemistry. 1971;8:871–4. [DOI] [PubMed]

12.

Tam JP, Zavala F. Multiple antigen peptide: A novel approach to increase detection sensitivity of synthetic peptides in solid-phase immunoassays. J Immunol Methods. 1989;124:53–61. [DOI] [PubMed]

13.

Vanier GS. Microwave-assisted solid-phase peptide synthesis based on the Fmoc protecting group strategy (CEM). Methods Mol Biol. 2013;1047:235–49. [DOI] [PubMed]

14.

Jespersen MC, Peters B, Nielsen M, Marcatili P. BepiPred-2.0: improving sequence-based B-cell epitope prediction using conformational epitopes. Nucleic Acids Res. 2017;45:W24–9. [DOI] [PubMed] [PMC]

15.

Saha S, Raghava GPS. Prediction methods for B-cell epitopes. Methods Mol Biol. 2007;409:387–94. [DOI] [PubMed]

16.

Kolaskar AS, Tongaonkar PC. A semi-empirical method for prediction of antigenic determinants on protein antigens. FEBS Lett. 1990;276:172–4. [DOI] [PubMed]

17.

Yao B, Zhang L, Liang S, Zhang C. SVMTriP: a method to predict antigenic epitopes using support vector machine to integrate tri-peptide similarity and propensity. PLoS One. 2012;7:e45152. [DOI] [PubMed] [PMC]

18.

El-Manzalawy Y, Dobbs D, Honavar V. Predicting linear B-cell epitopes using string kernels. J Mol Recognit. 2008;21:243–55. [DOI] [PubMed] [PMC]

19.

Andreatta M, Nielsen M. Gapped sequence alignment using artificial neural networks: application to the MHC class I system. Bioinformatics. 2016;32:511–7. [DOI] [PubMed] [PMC]

20.

Nielsen M, Lundegaard C, Worning P, Lauemøller SL, Lamberth K, Buus S, et al. Reliable prediction of T-cell epitopes using neural networks with novel sequence representations. Protein Sci. 2003;12:1007–17. [DOI] [PubMed] [PMC]

21.

Zhang H, Lund O, Nielsen M. The PickPocket method for predicting binding specificities for receptors based on receptor pocket similarities: application to MHC-peptide binding. Bioinformatics. 2009;25:1293–9. [DOI] [PubMed] [PMC]

22.

Stranzl T, Larsen MV, Lundegaard C, Nielsen M. NetCTLpan: pan-specific MHC class I pathway epitope predictions. Immunogenetics. 2010;62:357–68. [DOI] [PubMed] [PMC]

23.

Reynisson B, Alvarez B, Paul S, Peters B, Nielsen M. NetMHCpan-4.1 and NetMHCIIpan-4.0: improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data. Nucleic Acids Res. 2020;48:W449–54. [DOI] [PubMed] [PMC]

24.

Paul S, Sidney J, Sette A, Peters B. TepiTool: A Pipeline for Computational Prediction of T Cell Epitope Candidates. Curr Protoc Immunol. 2016;114:18.19.1–18.19.24. [DOI] [PubMed] [PMC]

25.

Ahmed SF, Quadeer AA, McKay MR. COVIDep: a web-based platform for real-time reporting of vaccine target recommendations for SARS-CoV-2. Nat Protoc. 2020;15:2141–2. [DOI] [PubMed] [PMC]

26.

Winkler DF, McGeer PL. Protein labeling and biotinylation of peptides during spot synthesis using biotin p-nitrophenyl ester (biotin-ONp). Proteomics. 2008;8:961–7. [DOI] [PubMed]

27.

Zerpa NC, Wide A, Noda J, Bermúdez H, Pabón R, Noya OO. Immunogenicity of synthetic peptides derived from Plasmodium falciparum proteins. Exp Parasitol. 2006;113:227–34. [DOI] [PubMed]

28.

Noya O, Alarcón de Noya B, Guzmán F, Bermúdez H. Immunogenicity of Sm32 synthetic peptides derived from the Schistosoma mansoni adult worm. Immunol Lett. 2003;88:211–9. [DOI]

29.

Hopp TP, Woods KR. Prediction of protein antigenic determinants from amino acid sequences. Proc Natl Acad Sci U S A. 1981;78:3824–8. [DOI] [PubMed] [PMC]

30.

Noya O, De Noya BA, Ballen DE, Bermúdez H, Bout D, Hoebeke J. Immunogenicity of synthetic peptides from the Sm31 antigen (cathepsin B) of the Schistosoma mansoni adult worms. Parasite Immunol. 2001;23:567–73. [DOI] [PubMed]

31.

Parker JM, Guo D, Hodges RS. New hydrophilicity scale derived from high-performance liquid chromatography peptide retention data: correlation of predicted surface residues with antigenicity and X-ray-derived accessible sites. Biochemistry. 1986;25:5425–32. [DOI] [PubMed]

32.

Kumar H, Kim P. Artificial intelligence in fusion protein three-dimensional structure prediction: Review and perspective. Clin Transl Med. 2024;14:e1789. [DOI] [PubMed] [PMC]

33.

Zou P, Chen WT, Sun T, Gao Y, Li LL, Wang H. Recent advances: peptides and self-assembled peptide-nanosystems for antimicrobial therapy and diagnosis. Biomater Sci. 2020;8:4975–96. [DOI] [PubMed]

34.

Ucar B, Acar T, Pelit Arayici P, Sen M, Derman S, Mustafaeva Z. Synthesis and Applications of Synthetic Peptides. Pept Synth. 2019. [DOI]

35.

Meloen RH, Langedijk JP, Langeveld JP. Synthetic peptides for diagnostic use. Vet Q. 1997;19:122–6. [DOI] [PubMed]

36.

Henninot A, Collins JC, Nuss JM. The Current State of Peptide Drug Discovery: Back to the Future? J Med Chem. 2018;61:1382–414. [DOI] [PubMed]

37.

Pérez Escoda MT. Diseño y síntesis de péptidos para el diagnóstico de la infección por el virus de la hepatitis G (GBV-C/HGV). [dissertation]. Barcelona: Universitat de Barcelona; 2007.

38.

Garay Pérez HE. Síntesis de péptidos modificados químicamente con posibles aplicaciones farmacéuticas [dissertation]. La Habana: Universidad de La Habana; 2012.

39.

Winkler DF, Campbell WD. The spot technique: synthesis and screening of peptide macroarrays on cellulose membranes. Methods Mol Biol. 2008;494:47–70. [DOI] [PubMed]

40.

Frank R. The SPOT-synthesis technique: Synthetic peptide arrays on membrane supports—principles and applications. J Immunol Methods. 2002;267:13–26. [DOI] [PubMed]

41.

Loomis-Price LD. Linear Epitope Mapping by the PEPSCAN Method. Methods Mol Med. 1999;17:293–307. [DOI] [PubMed]

42.

Volkmer R. Synthesis and application of peptide arrays: quo vadis SPOT technology. Chembiochem. 2009;10:1431–42. [DOI] [PubMed]

43.

Maupetit J, Derreumaux P, Tuffery P. PEP-FOLD: an online resource for de novo peptide structure prediction. Nucleic Acids Res. 2009;37:W498–503. [DOI] [PubMed] [PMC]

44.

Lorenzo MA, Pachón D, Maier A, Bermúdez H, Losada S, Toledo M, et al. Immunoinformatics and Pepscan strategies on the path of a peptide-based serological diagnosis of COVID19. J Immunol Methods. 2021;495:113071. [DOI] [PubMed] [PMC]

45.

Šimundić AM. Measures of Diagnostic Accuracy: Basic Definitions. EJIFCC. 2009;19:203–11. [PubMed] [PMC]

46.

Durango I, Losada S, Bermúdez H, Villalba J, Sulbaran Y, Jaspe RC, et al. Strong antibody reactivity to HIV-1 synthetic peptides in seropositive indigenous Warao people. Biomedica. 2025;45:267–76. Spanish. [DOI] [PubMed]

47.

Devesa M, de Saez A, León G, Sirit F, Cosson C, Bermúdez H, et al. Restricted isotypic antibody reactivity to hepatitis C virus synthetic peptides in immunocompromised patients. Clin Diagn Lab Immunol. 1999;6:279–81. [DOI] [PubMed] [PMC]

48.

Aguilar MS, Cosson C, Loureiro CL, Devesa M, Martínez J, Villegas L, et al. Prevalence of infection with hepatitis C virus in Venezuela, as assessed with an immuno-assay based on synthetic peptides. Ann Trop Med Parasitol. 2001;95:187–95. [PubMed]

49.

Gauna A, Losada S, Lorenzo M, Toledo M, Bermúdez H, D’Angelo P, et al. Use of Synthetic Peptides and Multiple Antigen Blot Assay in the Immunodiagnosis of Hepatitis C Virus Infection. Viral Immunol. 2018;31:568–74. [DOI] [PubMed]

50.

Gauna A, Losada S, Lorenzo M, Bermúdez H, Toledo M, Pérez H, et al. Synthetic peptides for the immunodiagnosis of hepatitis A virus infection. J Immunol Methods. 2015;427:1–5. [DOI] [PubMed]

51.

Requena JM, Soto M, Guzman F, Maekelt A, Noya O, Patarroyo ME, et al. Mapping of antigenic determinants of the T. cruzi HSP70 in chagasic and healthy individuals. Mol Immunol. 1993;30:1115–21. [DOI] [PubMed]

52.

Thomas MC, Fernández-Villegas A, Carrilero B, Marañón C, Saura D, Noya O, et al. Characterization of an immunodominant antigenic epitope from Trypanosoma cruzi as a biomarker of chronic Chagas’ disease pathology. Clin Vaccine Immunol. 2012;19:167–73. [DOI] [PubMed] [PMC]

53.

Noya O, de Noya BA, Ballén D, Zerpa N, Colmenares C, Losada S, et al. Use of synthetic peptides derived from adult worm proteins of Schistosoma mansoni, in the diagnosis of schistosomiasis. Mem Inst Oswaldo Cruz. 1998;93:157–8. [DOI] [PubMed]

54.

Noya O, Alarcón de Noya B, Losada S, Colmenares C, Guzmán C, Lorenzo MA, et al. Laboratory diagnosis of Schistosomiasis in areas of low transmission: a review of a line of research. Mem Inst Oswaldo Cruz. 2002;97:167–9. [DOI] [PubMed]

55.

Sulbarán GS, Ballen DE, Bermúdez H, Lorenzo M, Noya O, Cesari IM. Detection of the Sm31 antigen in sera of Schistosoma mansoni- infected patients from a low endemic area. Parasite Immunol. 2010;32:20–8. [DOI] [PubMed]

56.

Cesari IM, Sulbaran G, Ballen D, Bermudez H, Noya O. Development of an immunocapture assay to detect circulating Sm31 (Cat B) antigen of Schistosoma mansoni. 8th International Symposium of Schistosomiasis Recife Brazil. 2001. pp. 8.

57.

Ortiz Princz D, De Sousa E, Kosak E, López R, Lorenzo A, Bermudez H, et al. Inmunodiagnóstico empleando péptidos sintéticos de CagA para el estudio de la infección por Helicobacter pylori [Internet]. [cited 2025 Feb 9]. Available from: https://revistagen.com/index.php/GEN/article/view/509/pdf

58.

Chen J, Wang L, Chen JJ, Sahu GK, Tyring S, Ramsey K, et al. Detection of antibodies to human immunodeficiency virus (HIV) that recognize conformational epitopes of glycoproteins 160 and 41 often allows for early diagnosis of HIV infection. J Infect Dis. 2002;186:321–31. [DOI] [PubMed]

59.

Borras-Cuesta F, Fedon Y, Petit-Camurdan A. Enhancement of peptide immunogenicity by linear polymerization. Eur J Immunol. 1988;18:199–202. [DOI] [PubMed]

60.

Costa-Mattioli M, Cristina J, Romero H, Perez-Bercof R, Casane D, Colina R, et al. Molecular evolution of hepatitis A virus: a new classification based on the complete VP1 protein. J Virol. 2002;76:9516–25. [DOI] [PubMed] [PMC]

61.

Emerson SU, Huang YK, Nguyen H, Brockington A, Govindarajan S, St Claire M, et al. Identification of VP1/2A and 2C as virulence genes of hepatitis A virus and demonstration of genetic instability of 2C. J Virol. 2002;76:8551–9. [DOI] [PubMed] [PMC]

62.

Haro I, Pérez S, García M, Chan WC, Ercilla G. Liposome entrapment and immunogenic studies of a synthetic lipophilic multiple antigenic peptide bearing VP1 and VP3 domains of the hepatitis A virus: a robust method for vaccine design. FEBS Lett. 2003;540:133–40. [DOI] [PubMed]

63.

Kang JA, Funkhouser AW. A proposed vestigial translation initiation motif in VP1 of hepatitis A virus. Virus Res. 2002;87:11–9. [DOI] [PubMed]

64.

Byun KS, Kim JH, Song KJ, Baek LJ, Song JW, Park SH, et al. Molecular epidemiology of hepatitis A virus in Korea. J Gastroenterol Hepatol. 2001;16:519–24. [DOI] [PubMed]

65.

Nenonen NP, Hernroth B, Chauque AA, Hannoun C, Bergström T. Detection of hepatitis A virus genotype IB variants in clams from Maputo Bay, Mozambique. J Med Virol. 2006;78:896–905. [DOI] [PubMed]

66.

Rodrigues L, Pista A, Oliveira A, Agua-Doce I, Manita C, Paixão MT. Molecular epidemiology of hepatitis A virus in a group of Portuguese citizens living in Lisbon area. J Med Virol. 2007;79:483–7. [DOI] [PubMed]

67.

Lorenzo MA, Gauna AN, Herrera J, Bermúdez H, Losada S, Noya O, et al. In silico modeling and structural analysis of asparaginyl endopeptidase of schistosoma mansoni (Sm32): Immunological and drug target implications. Comput Biol Chem. 2019;78:18–27. [DOI] [PubMed]

68.

Losada S, Chacón N, Colmenares C, Bermúdez H, Lorenzo A, Pointier JP, et al. Schistosoma: cross-reactivity and antigenic community among different species. Exp Parasitol. 2005;111:182–90. [DOI] [PubMed]

69.

Murugesan K, Jagannathan P, Pham TD, Pandey S, Bonilla HF, Jacobson K, et al. Interferon-γ Release Assay for Accurate Detection of Severe Acute Respiratory Syndrome Coronavirus 2 T-Cell Response. Clin Infect Dis. 2021;73:e3130–2. [DOI] [PubMed] [PMC]

70.

Warren JR, Marshall B. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet. 1983;1:1273–5. [PubMed]

71.

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. International Agency for Research on Cancer; 1994. pp. 1–241.

72.

Costa LCMC, das Graças Carvalho M, La Guárdia Custódio Pereira AC, Teixeira Neto RG, Andrade Figueiredo LC, Barros-Pinheiro M. Diagnostic Methods for Helicobacter pylori. Med Princ Pract. 2024;33:173–84. [DOI] [PubMed] [PMC]

73.

Tramontano A. Identificación de epítopos conformacionales. Biotecnol Apl. 2001;18:91–3.

74.

Sun P, Ju H, Liu Z, Ning Q, Zhang J, Zhao X, et al. Bioinformatics resources and tools for conformational B-cell epitope prediction. Comput Math Methods Med. 2013;2013:943636. [DOI] [PubMed] [PMC]

75.

Solihah B, Azhari A, Musdholifah A. Enhancement of conformational B-cell epitope prediction using CluSMOTE. PeerJ Comput Sci. 2020;6:e275. [DOI] [PubMed] [PMC]

76.

Arbour CA, Mendoza LG, Stockdill JL. Recent advances in the synthesis of C-terminally modified peptides. Org Biomol Chem. 2020;18:7253–72. [DOI] [PubMed] [PMC]

77.

Algar S, Martín-Martínez M, González-Muñiz R. Evolution in non-peptide α-helix mimetics on the road to effective protein-protein interaction modulators. Eur J Med Chem. 2021;211:113015. [DOI] [PubMed]

78.

Ortega-Rodriguez U, Portillo S, Ashmus RA, Duran JA, Schocker NS, Iniguez E, et al. Purification of Glycosylphosphatidylinositol-Anchored Mucins from Trypanosoma cruzi Trypomastigotes and Synthesis of α-Gal-Containing Neoglycoproteins: Application as Biomarkers for Reliable Diagnosis and Early Assessment of Chemotherapeutic Outcomes of Chagas Disease. Methods Mol Biol. 2019;1955:287–308. [DOI] [PubMed] [PMC]

79.

De Noya BA, Spencer L, Noya O. Pre- and post-treatment immunodiagnostic evaluation in human schistosomiasis mansoni. Mem Inst Oswaldo Cruz. 1992;87:271–6. [DOI] [PubMed]

80.

Patarroyo ME, Amador R, Clavijo P, Moreno A, Guzman F, Romero P, et al. A synthetic vaccine protects humans against challenge with asexual blood stages of Plasmodium falciparum malaria. Nature. 1988;332:158–61. [DOI] [PubMed]