A. Asín

A. Eguskiza

A. Martinez

C. Bretón

C. Nativi

E. Jiménez-Moreno

F. Corzana

G. Malerba

J. M. Peregrina

M. Ghirardello

R. Fiammengo

R. Hurtado-Guerrero

V. Mangini

English

Repositorio de Universidad de La Rioja

 ABSTRACT BOOK    XXIX RSEQ  Biennial Meeting in Organic Chemistry Santa Cruz de Tenerife, June 26-28, 2024                   OC30  ORAL COMMUNICATION Identification of Tumor-Linked Pancreatic Cancer Autoantibodies in Patients’ sera Through Engineered Glycopeptides  M. Ghirardello,a A. Asín,a A. Eguskiza,b V. Mangini,c C. Bretón,a E. Jiménez-Moreno,a C. Nativi,d R. Hurtado-Guerrero,e J. M. Peregrina,a G. Malerba,f A. Martinez,g R. Fiammengo,b,c F. Corzanaa aDepartamento de Química. Instituto de Investigación en Química de la Universidad de La Rioja (IQUR). Universidad de La Rioja, 26006 Logroño (La Rioja). Spain. bDepartment of Biotechnology, University of Verona, 37134 Verona, Italy. cCenter for Biomolecular Nanotechnologies@UniLe, Istituto Italiano di Tecnologia (IIT), 73010 Arnesano, Lecce, Italy.  dDepartment of Chemistry, University of Florence, 50019 Sesto Fiorentino (FI), Italy. eInstitute of Biocomputation and Physics of Complex Systems, University of Zaragoza, Mariano Esquillor s/n, Campus Rio Ebro, Edificio I+D, 50018 Zaragoza, Spain. fGM Lab, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, 37134, Italy. gAngiogenesis Group, Oncology Area, Center for Biomedical Research of La Rioja (CIBIR), 26006 Logroño, Spain. mattia.ghirardello@unirioja.es  Pancreatic cancer ranks as the seventh leading cause of cancer-related mortality worldwide, often detected only in advanced stages, hampering treatment options.1 The emergence of anti-MUC1 autoantibodies in early cancer stages suggests promise for early detection methods.2 Building upon this concept, we employed a structure-guided approach to engineer the GalNAc motif in MUC1 glycopeptide sequences, providing ligands with both high and low-affinity used as controls against two commercial anti-MUC1 antibodies (SM3 and 5E5).3 Validation via surface plasmon resonance and molecular dynamics simulations confirmed distinct affinities. These antigens were presented on the surface of gold nanoparticles4 and employed in a dot-blot assay to detect autoantibodies in samples from pancreatic cancer patients and healthy individuals. Our findings demonstrated that nanoparticle probes featuring high-affinity glycopeptides for the 5E5 antibody effectively distinguished between pancreatic cancer cases and healthy individuals. In contrast, those with low-affinity glycopeptides for 5E5 or high-affinity glycopeptides for SM3 did not yield such discrimination. Notably, the optimal nanoparticle probe exhibited superior true and false positive rates compared to conventional clinical biomarkers like CA19-9 and carcinoembryonic antigen (CEA). These results underscore the potential of chemically engineered glycopeptide derivatives with enhanced affinity for specific anti-MUC1 antibodies for their applications in innovative diagnostic tools for pancreatic cancer detection.   Acknowledgments: Agencia Estatal de Investigación (PID2021-127622OB-I00 and PDC2022-133725-C21), Asociación Española Contra el Cáncer (INNOVA 2023). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 101034288.  References: 1. Sung H.; et al. CA Cancer. J. Clin. 2021, 71, 209. 2. (a) Zhuang, L.; et al. Int. J. Cancer 2023, 152, 1013. (b) Tan, H. T.; et al. FEBS J. 2009, 276, 6880. (c) Wu, J.; et al. Autoimmun. Rev. 2017, 16, 1270. (d) Karsten, U.; et al. Tumor Biol. 2005, 26, 217. 3. (a) V. J. Somovilla; et al. J. Am. Chem. Soc. 2017, 139, 18255. (b) I. Compañón; et al. J. Am. Chem. Soc., 2019, 141, 4063. (c) I. Bermejo; et al. JACS Au 2024, 4, 150. 4. (a) Maus, L.; et al. ACS Nano 2010, 4, 6617. (b) Mangini, V.; et al. Bioconjugate Chem. 2020, 31, 74.   

Identification of Tumor-Linked Pancreatic Cancer Autoantibodies in Patients’ sera Through Engineered Glycopeptides

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Identification of Tumor-Linked Pancreatic Cancer Autoantibodies in Patients’ sera Through Engineered Glycopeptides

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