Scholarship 24/05373-4 - - BV FAPESP
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Synthesis, characterization and purification of peptide complexes with the chelating agent DOTA for future radiolabeling processes with Ga-68.

Grant number: 24/05373-4
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Start date until: May 01, 2024
End date until: April 30, 2025
Field of knowledge:Biological Sciences - Biochemistry - Chemistry of Macromolecules
Principal Investigator:Luciana Malavolta Quaglio
Grantee:Leonardo Yumoto Carvalheira
Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:21/10265-8 - Cancer Theranostics Innovation Center (CancerThera), AP.CEPID

Abstract

Due to the significant biological importance of peptides, such as their involvement in physiological responses and their substantial potential for disease treatment, numerous studies have been conducted employing these molecules, including tumorigenic diseases. The great potential of peptides is attributed to several characteristics, including non-immunogenicity and minimal side effects, low toxicity, high blood clearance, facilitated tissue penetration, high affinity for target tissues, as well as their capacity for rapid and cost-effective synthesis. The class of peptides that inhibit signaling pathways is encompassed within Molecular Targeted Therapies, with the majority of cases targeting receptors overexpressed in tumors. In this context, many peptides based on the RGD (Arg-Gly-Asp) fragment, which exhibit high affinity for the integrin adhesion molecule, and peptides with affinity for EGF receptors have been evaluated. It is known that these receptors are overexpressed on the surface of cells in a variety of human cancers (lung, prostate, colon, breast, and glioblastoma), and due to their functions related to tumor growth, differentiation, and migration, they are considered specific targets for accessing tumorigenic cells. Recently, our group demonstrated the radiochemical and biological properties of the peptides EEEEYFELV and GRGDYD, which have high affinity for EGFR and the integrin molecule, respectively, by evaluating the binding and internalization affinity of these peptides in tumorigenic cells related to glioblastoma. The present work aims to synthesize, purify, and characterize the peptide molecules EEEEYFELV and GRGDYV modified with the chelating agent DOTA for future radiolabeling with the Ga-68 radioisotope. The proposed peptides will be synthesized through solid-phase peptide synthesis using the Fmoc/tBut strategy, and purification will be performed by preparative high-performance liquid chromatography (HPLC), while analytical characterization will entail analytical HPLC and mass spectrometry.

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