Synthesis and antimicrobial evaluation of two peptide LyeTx I derivatives modified with the chelating agent HYNIC for radiolabeling with technetium-99m

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dc.creatorLeonardo Lima Fuscaldi
dc.creatorDaniel Moreira Dos Santos
dc.creatorNatália Gabriela Silva Pinheiro
dc.creatorRaquel Silva Araújo
dc.creatorAndré Luís Branco de Barros
dc.creatorJarbas Magalhães Resende
dc.creatorSimone Odília Antunes Fernandes
dc.creatorMaria Elena de Lima
dc.creatorValbert Nascimento Cardoso
dc.date.accessioned2022-03-29T18:52:48Z
dc.date.accessioned2025-09-08T23:02:26Z
dc.date.available2022-03-29T18:52:48Z
dc.date.issued2016
dc.format.mimetypepdf
dc.identifier.doi10.1186/s40409-016-0070-y
dc.identifier.issn16789199
dc.identifier.urihttps://hdl.handle.net/1843/40564
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofJournal of Venomous Animals and Toxins including Tropical Diseases
dc.rightsAcesso Aberto
dc.subjectQuímica
dc.subject.otherSeptic and aseptic inflammation
dc.subject.otherDifferential diagnosis
dc.subject.otherAntimicrobial peptides
dc.subject.otherLyeTx I derivatives
dc.subject.otherMALDI-ToF-MS
dc.subject.otherRP-HPLC
dc.subject.otherTechnetium-99m
dc.subject.otherHYNIC
dc.subject.otherEDDA
dc.subject.otherTricine
dc.titleSynthesis and antimicrobial evaluation of two peptide LyeTx I derivatives modified with the chelating agent HYNIC for radiolabeling with technetium-99m
dc.typeArtigo de periódico
local.citation.epage8
local.citation.issue16
local.citation.spage1
local.citation.volume22
local.description.resumoBackground: Current diagnostic methods and imaging techniques are not able to differentiate septic and aseptic inflammation. Thus, reliable methods are sought to provide this distinction and scintigraphic imaging is an interesting option, since it is based on physiological changes. In this context, radiolabeled antimicrobial peptides have been investigated as they accumulate in infectious sites instead of aseptic inflammation. The peptide LyeTx I, from the venom of Lycosa erythrognatha, has potent antimicrobial activity. Therefore, this study aimed to synthesize LyeTx I derivatives with the chelating compound HYNIC, to evaluate their antimicrobial activity and to radiolabel them with 99mTc. Methods: Two LyeTx I derivatives, HYNIC-LyeTx I (N-terminal modification) and LyeTx I-K-HYNIC (C-terminal modification), were synthesized by Fmoc strategy and purified by RP-HPLC. The purified products were assessed by RP-HPLC and MALDI-ToF-MS analysis. Microbiological assays were performed against S. aureus (ATCC® 6538) and E. coli (ATCC® 10536) in liquid medium to calculate the MIC. The radiolabeling procedure of LyeTx I-K-HYNIC with 99mTc was performed in the presence of co-ligands (tricine and EDDA) and reducing agent (SnCl2 . 2H2O), and standardized taking into account the amount of peptide, reducing agent, pH and heating. Radiochemical purity analysis was performed by thin-layer chromatography on silica gel strips and the radiolabeled compound was assessed by RP-HPLC and radioactivity measurement of the collected fractions. Data were analyzed by ANOVA, followed by Tukey test (p-values < 0.05). Results: Both LyeTx I derivatives were suitably synthesized and purified, as shown by RP-HPLC and MALDI-ToF-MS analysis. The microbiological test showed that HYNIC-LyeTx I (N-terminal modification) did not inhibit bacterial growth, whereas LyeTx I-K-HYNIC (C-terminal modification) showed a MIC of 5.05 μmol. L−1 (S. aureus) and 10.10 μmol. L−1 (E. coli). Thus, only the latter was radiolabeled with 99mTc. The radiochemical purity analysis of LyeTx I-K-HYNIC-99mTc showed that the optimal radiolabeling conditions (10 μg of LyeTx I-K-HYNIC; 250 μg of SnCl2 . 2H2O; pH = 7; heating for 15 min) yielded a radiochemical purity of 87 ± 1 % (n = 3). However, RP-HPLC data suggested 99mTc transchelation from LyeTx I-K-HYNIC to the co-ligands (tricine and EDDA). Conclusions: The binding of HYNIC to the N-terminal portion of LyeTx I seems to affect its activity against bacteria. Nevertheless, the radiolabeling of the C-terminal derivative, LyeTx I-K-HYNIC, must be better investigated to optimize the radiolabeled compound, in order to use it as a specific imaging agent to distinguish septic and aseptic inflammation.
local.publisher.countryBrasil
local.publisher.departmentFAR - DEPARTAMENTO DE ALIMENTOS
local.publisher.departmentFAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICAS
local.publisher.departmentICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIA
local.publisher.departmentICX - DEPARTAMENTO DE QUÍMICA
local.publisher.initialsUFMG
local.url.externahttps://www.scielo.br/j/jvatitd/a/bR6xtMwsLbjrR9CY6XrrzKN/?lang=en#

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