Study on the Synthesis,Structural Characterization and Activity of Fluorine-Containing Borneol Ester / 广州中医药大学学报

Objective Four fluorine-containing borneol ester were synthesized and analyzed for structure characterization and activity.Methods Four fluorine-containing borneol ester derivatives were synthesized by the reaction of fluorinated carboxylic acid and borneol by using p-toluenesulfonic acid as catalyst,and the structures of borneol esters were characterized by 1HNMR and 13CNMR.Molecular docking of the four fluorine-containing borneol ester with P-glycoprotein was carried out by Autodock Vina software.Results Four fluorine-containing borneol ester,bornyl 2-chloro-4-trifluoromethyl benzoate,bornyl 2-chloro-5-fluoro benzoate,bornyl 2-chloro-5-trifluoromethyl benzoate,bornyl 3-trifluoromethyl benzoate,were synthesized.The structures of the borneol ester were confirmed by 1HNMR and 13CNMR.4 fluorine-containing borneol ester had good binding ability with P-glycoprotein.Conclusion Four borneol ester compounds were synthesized,and the borneol ester enriched the types of borneol derivatives,which is of reference value for expanding the application range of borneol.

Development and Synthesis of Activity-based and Affinity-based Ubiquitin Probes / 生物化学与生物物理进展

Ubiquitination, a diverse post-translational modification, is carried out by enzymes including E1-activating enzymes, E2-conjugating enzymes, E3 ligases, and deubiquitinating enzymes (DUBs). Ubiquitin itself possesses 7 lysine residues and N-terminal methionine, allowing for the formation of polyubiquitin chains with different lengths and linkages. These chains exhibit various topologies that can be recognized by proteins containing ubiquitin-binding domain, thereby transmitting distinct cellular signals. To unravel the physiological mechanisms associated with ubiquitin, numerous ubiquitin probes have been developed. This review provides an overview of recent advancements in the field of ubiquitin probes, focusing on activity-based and affinity-based probes. Activity-based probes are designed to covalently bind to DUBs, E1s, or E3s, enabling the identification and characterization of these enzymes. Affinity-based probes, on the other hand, selectively bind to ubiquitin-binding domains, facilitating the identification of proteins that interact with ubiquitin. Moreover, this review comprehensively discusses the synthetic methodologies employed for the acquisition of ubiquitin probes. These includes meticulous discussions on the synthesis of individual monomeric modules, the establishment of isopeptide linkages, as well as the incorporation of reactive functional groups. Additionally, the review explores the emerging area of cell-penetrating ubiquitin probes and highlights their latest applications in living cells. These probes incorporate cell-penetrating peptides to enable their internalization into cells, allowing for direct visualization and manipulation of ubiquitin-modified proteins within their native environment. Overall, this review offers insights into the design, synthesis, and applications of ubiquitin probes, highlighting their significance in elucidating ubiquitin-mediated cellular processes.

Advances in physiological activities and synthesis of β-nicotinamide mononucleotide / 生物工程学报

Nicotinamide mononucleotide (NMN) is one of the key precursors of coenzyme Ⅰ (NAD+). NMN exists widely in a variety of organisms, and β isomer is its active form. Studies have shown that β-NMN plays a key role in a variety of physiological and metabolic processes. As a potential active substance in anti-aging and improving degenerative and metabolic diseases, the application value of β-NMN has been deeply explored, and it is imminent to achieve large-scale production. Biosynthesis has become the preferred method to synthesize β-NMN because of its high stereoselectivity, mild reaction conditions, and fewer by-products. This paper reviews the physiological activity, chemical synthesis as well as biosynthesis of β-NMN, highlighting the metabolic pathways involved in biosynthesis. This review aims to explore the potential of improving the production strategy of β-NMN by using synthetic biology and provide a theoretical basis for the research of metabolic pathways as well as efficient production of β-NMN.

Synthesis and preliminary clinical application of Al 18F-FAPI-74 / 中华核医学与分子影像杂志

Objective:To automatically synthesize Al 18F-fibroblast activation protein inhibitor (FAPI)-74, and explore its value of clinical application. Methods:Al 18F-FAPI-74 was synthesized automatically by the commercial synthesis module CFN-MPS-100, and its yield, radiochemical purity and stability were determined. Sixteen normal Kunming (KM) mice were randomly divided into 4 groups and euthanized at 10, 30, 60 and 90 min after Al 18F-FAPI-74 injection, and the biodistribution was measured. MicroPET/CT dynamic scanning (60 min) was performed in 5 rat pancreatic tumor-bearing BALB/c nude mice to observe the tumor uptake. Al 18F-FAPI-74 PET/CT imaging was performed on 3 volunteers (1 male, 2 females; age: 37, 41, 43 years) to evaluate the clinical application value of Al 18F-FAPI-74. Results:The automated synthesis time of Al 18F-FAPI-74 was about 35 min, with the synthesis yield of (21.34±3.86)% (without attenuation correction, n=5) and the radiochemical purity more than 99%. The radiochemical purity was still more than 96% after placement at 37 ℃ for 6 h. Biodistribution in normal mice and microPET/CT dynamic scanning in tumor-bearing nude mice showed that consistently high uptake in the kidneys and bladder, and the tumor uptake was the highest at 20 min, and the maximum tumor-to-muscle ratio was 3.16±0.01 at 60 min. PET/CT imaging on volunteers showed that there was a small amount of uptake in myocardium, most organs such as the liver and lung had background uptake, and the maximum SUV max of persistent high uptake of tumor was 17.08. Conclusions:Al 18F-FAPI-74 has the advantages of simple synthesis, high yield, stable quality and good imaging performance in mice and volunteers. It is a kind of imaging agent that meets the requirements of clinical diagnosis.

Advances of the novel immunosuppressant brasilicardin A / 生物工程学报

Brasilicardin A (BraA) is a natural diterpene glycoside isolated from the pathogenic actinomycete Nocardia brasiliensis IFM 0406 with highly potent immunosuppressive activity (IC50=0.057 μg/mL). BraA potently inhibits the uptake of amino acids that are substrates for amino acid transport system L of T cells, which is different from the existing clinical immunosuppressants. BraA is more potent in a mouse mixed lymphocyte reaction and less toxic against various human cell lines compared with the known clinical immunosuppressants, such as cyclosporin A, ascomycin and tacrolimus. Therefore, BraA attracted more attention as a new promising immunosuppressant. However, the development of this promising immunosuppressant as drug for medical use is so far hindered because BraA has the unusual and synthetically challenging skeleton and shows the low-yield production in the natural pathogenic producer. This review introduces the molecular structure of BraA, its activity, mechanism of action, chemical synthesis of BraA analogs, heterologous expression of gene cluster, and an application of combining microbial and chemical synthesis for production of BraA, with the aim to facilitate the efficient production of BraA and its analogs.

Enhancing glass ionomer cement features by using the calcium phosphate nanocomposite

Abstract This study showed the synthesis of Glass ionomer cements (GIC) modified with calcium phosphate nanoparticles (nCaP). The nCaP/GIC were submitted to mechanical compression and diametral tensile tests. The biocomposite were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR). Cytotoxicity and cell viability tests were performed on the human bone marrow mesenchymal stem cells using a 3-(4,5-dimethylthiazol-2yl)2,5-diphenyl- tetrazolium-bromide assay and LIVE/DEAD assays. Statistically significant differences were observed for mechanical properties (Kruskal-Wallis, p<0.001), nCaP/GIC showed higher resistance to compression and diametral traction. The SEM analyses revealed a uniform distribution nCaP in the ionomer matrix. The EDX and XRD results indicated that hydroxyapatite and calcium β-triphosphate phases. The FTIR spectra revealed the asymmetric band of ν3PO43- between 1100-1030cm-1 and the vibration band associated with ν1PO43- in 963cm-1 associated with nCaP. The nCaP/GIC presented response to adequate cell viability and non-cytotoxic behavior. Therefore, the new nCaP/GIC composite showed great mechanical properties, non-cytotoxic behavior, and adequate response to cell viability with promising dental applications.

Resumo Este estudo apresenta a síntese de cimentos de ionômero de vidro (GIC) modificados com nanopartículas de fosfato de cálcio (nCaP). Os nCaP / GIC foram submetidos a ensaios mecânicos de compressão e tração diametral. Os biocompósitos foram caracterizados por microscopia eletrônica de varredura (MEV), espectroscopia de energia dispersiva de raios-X (EDX), difração de raios-X (XRD) e espectroscopia de infravermelho com transformada de Fourier (FTIR). Os testes de citotoxicidade e viabilidade celular foram realizados em células-tronco mesenquimais da medula óssea humana usando um ensaio de 3- (4,5-dimetiltiazol-2-il) 2,5-difeniltetrazólio-brometo e ensaios LIVE / DEAD. Diferenças estatisticamente significativas foram observadas para as propriedades mecânicas (Kruskal-Wallis, p <0,001), nCaP / GIC apresentou maior resistência à compressão e tração diametral. As análises de SEM revelaram uma distribuição uniforme de nCaP na matriz do ionômero. Os resultados de EDX e DRX indicaram fases de hidroxiapatita e β-trifosfato de cálcio. Os espectros de FTIR revelaram a banda assimétrica de ν3PO4 3- entre 1100-1030cm-1 e a banda de vibração associada a ν1PO4 3- em 963cm-1 associada a nCaP. O nCaP / GIC apresentou resposta adequada à viabilidade celular e comportamento não citotóxico. Portanto, o novo compósito nCaP / GIC apresentou ótimas propriedades mecânicas, comportamento não citotóxico e resposta adequada à viabilidade celular com promissoras aplicações odontológicas.

Indicadores hematológicos en pacientes con infección por SARS COV-2 / Hematological indicators in patients with SARS COV-2 infection

Objetivo: Analizar los indicadores hematológicos en pacientes con infección por SARS COV-2. Método: Observacional de tipo descriptiva. Resultados: Se ha encontrado la existencia de un patrón común de exámenes anormales del recuento leucocitario con Neutrófilos elevados en 43.69 % (neutrofilia) y los linfocitos, pero por debajo de los valores normales (linfopenia) en un 20.16 %. Además de monocitopenia en un 13.44%. Conclusión: La detección de Proteína C reactiva elevada y neutrofilia se relaciona con casos severos de COVID-19 en pacientes adultos. Ambas pruebas combinadas tienen una alta especificidad y sensibilidad para predicción temprana de casos se veros de COVID -19.

Objective: To analyze hematological indicators in patients with SARS COV-2 infection. Methods: Descriptive observational study. Results: A common pattern of abnormal leukocyte count tests was found with elevated neutrophils in 43.69% (neutrophilia) and lymphocytes, but below normal values (lymphopenia) in 20.16%. In addition to monocytopenia in 13.44%. Conclusion: The detection of elevated C-reactive protein and neutrophilia is associated with severe cases of COVID-19 in adult patients. Both tests combined have high specificity and sensitivity for early prediction of severe cases of COVID -19.

Automatic synthesis of 18F-fallypride and evaluation of microPET/CT imaging effect / 中华核医学与分子影像杂志

Objective:To establish an optimized automatic synthesis method of 18F-fallypride, and evaluate its biodistribution and microPET/CT characteristics. Methods:18F-fallypride was automatically prepared by AIO synthesis module and disposable cassette & reagents kit. The crude product was purified by a dedicated coupled column (HLB+ Alumin-N) to obtain the final product. Radiochemical purity and radiolabeling yield were determined. Parkinson′s disease (PD) model mice and rats were established. The radioactive distribution of different organs of PD model mice ( n=24) were monitored. The distribution process of the agent in the SD rat brain (PD model, n=6; normal rat, n=6) were evaluated by microPET/CT imaging. Results:The radiochemical yield of 18F-fallypride synthesized by automatic synthesis module was stable at (10±1)% ( n=5, no decay corrected). The total synthesis time was about 40 min. The radiochemical purity of 18F-fallypride was more than 95%, and the radiochemical purities were also over 95% after being stored in saline and serum for 120 min at room temperature. 18F-fallypride was mainly excreted by the kidneys, and it was less radioactive intake in the liver and spleen in PD mice. MicroPET/CT imaging showed that higher accumulation of 18F-fallypride was noted in corpus striatum and the SUV ratio of PD group was lower than that of control group (5.00±0.93 vs 6.53±1.96). Conclusion:18F-fallypride can be successfully prepared automatically by improved multifunctional module, with the advantages of convenient preparation, stable radiochemical yield, satisfying purity and quality control, so it can be used in the follow-up standardized production of Good Manufacture Practice (GMP) system.

Chemical synthesis of a synthetically useful L-galactosaminuronic acid building block / 中国天然药物

Most bacterial cell surface glycans are structurally unique, and have been considered as ideal target molecules for the developments of detection and diagnosis techniques, as well as vaccines. Chemical synthesis has been a promising approach to prepare well-defined oligosaccharides, facilitating the structure-activity relationship exploration and biomedical applications of bacterial glycans. L-Galactosaminuronic acid is a rare sugar that has been only found in cell surface glycans of gram-negative bacteria. Here, an orthogonally protected L-galactosaminuronic acid building block was designed and chemically synthesized. A synthetic strategy based on glycal addition and TEMPO/BAIB-mediated C6 oxidation served well for the transformation of commercial L-galactose to the corresponding L-galactosaminuronic acid. Notably, the C6 oxidation of the allyl glycoside was more efficient than that of the selenoglycoside. In addition, a balance between the formation of allyl glycoside and the recovery of selenoglycoside was essential to improve efficiency of the NIS/TfOH-catalyzed allylation. This synthetically useful L-galactosaminuronic acid building block will provide a basis for the syntheses of complex bacterial glycans.

Chemical approaches towards installation of rare functional groups in bacterial surface glycans / 中国天然药物

Bacterial surface glycans perform a diverse and important set of biological roles, and have been widely used in the treatment of bacterial infectious diseases. The majority of bacterial surface glycans are decorated with diverse rare functional groups, including amido, acetamidino, carboxamido and pyruvate groups. These functional groups are thought to be important constituents for the biological activities of glycans. Chemical synthesis of glycans bearing these functional groups or their variants is essential for the investigation of structure-activity relationships by a medicinal chemistry approach. To date, a broad choice of synthetic methods is available for targeting the different rare functional groups in bacterial surface glycans. This article reviews the structures of naturally occurring rare functional groups in bacterial surface glycans, and the chemical methods used for installation of these groups.

Research progress on indanomycin natural products / 药学实践杂志

Indanomycins are a class of secondary metabolites of microorganisms with a trans-tetrahydroindan (indane) ring. These compounds generally have good antibacterial, insecticidal and antitumor biological activities, which have caused wide interest for medicinal chemists and biologists. This review summarizes the research progress of the discovery, biological activity, chemical synthesis and biosynthesis of indanomycin compounds since 1979 and provides scientific reference for the research and development of indanomycin antibiotics.

Improved synthesis process of optical-magnetic bimodal probe of Gd-4, 7-Bis-carboxymethyl-10-(2-fluoresceinthioureaethyl)-1, 4, 7, 10-tetraaza-cyclododec-1-yl-acetic acid complexes / 北京大学学报(医学版)

OBJECTIVE@#To improve the methods to synthesize and purify of optical-magnetic bimodal molecular probe of Gd-[4, 7-Bis-carboxymethyl-10-(2-fluorescein thioureaethyl)-1, 4, 7, 10-tetraaza-cyclododec-1-yl]-acetic acid complexes.@*METHODS@#Target compound (7), optical-magnetic bimodal molecular molecular probe, was synthesized by the use of 1, 4, 7, 10-tetraazacyclododecane (1) as starting material via substitution reaction, hydrolysis reaction, coupling reaction and complexation reaction with metal.@*RESULTS@#The synthetic route of Gd-[4, 7-Bis-carboxymethyl-10-(2-fluoresceinthioureaethyl)-1, 4, 7, 10-tetraaza-cyclododec-1-yl]-acetic acid complexes was improved. The optical-magnetic bimodal molecular probes were synthesized by substitution reaction, hydrolysis reaction, coupling reaction and complex reaction with metal respectively. For the improved route, the total yield could reach 34.6% which was higher than the original route (18.0%). The structures of those compounds were identified by 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, and mass spectrometry. The improved route could avoid the uncontrollable disadvantage of the substitution reaction, this process could reduce the formation of impurities and made the purification process easier, and in the aspect of purification and separation, the preparative high-performance liquid chromatography with less sample loading and high cost was improved to a column chromatography with many sample loads and being easy to operate. Therefore, the use of column chromatography could be more conducive to mass production of the optical-magnetic bimodal molecular molecular probe.@*CONCLUSION@#The improved synthetic route improves the controllability of the reaction conditions and makes it easier to purify and separate the compounds. At the same time, the improved synthetic route can increase the total yield significantly. The optical-magnetic bimodal molecular probe can combine the living magnetic resonance imaging with the in vitro optical imaging to realize the dual synchronous detection of magneto-optics, so that the detection results of the living magnetic resonance imaging and the in vitro optical imaging are mutually verified. In other words, this synthetic optical-magnetic bimodal molecular probe will make the experimental results more accurate and reliable. In subsequent biological experimental studies, the optical-magnetic bimodal molecular probe can be applied to related research of brain structure and function, and the probe can be used for the brain-related diseases researches, such as brain tumors. after intravenous administration, and thus the optical-magnetic bimodal molecular probe can play an important role in medical treatment of brain tumors and cerebrovascular diseases.

Synthesis of 18 F-PSMA-1007 by one-step method and PET/CT imaging in prostate cancer / 中华核医学与分子影像杂志

Objective To synthesize and analyze 18 F-prostate specific membrane antigen ( PSMA)-1007, followed by its imaging in prostate cancer. Methods Based on one-step method, 18 F-PSMA-1007 was produced by the CFN-MPS-200 automatic synthesis module and its quality analysis was conducted. 18 F-PSMA-1007 PET/CT imaging was performed in a prostate cancer patient (66 years old). Results The syn-thesis time of 18F-PSMA-1007 was about 50 min, and the radiochemical yield was (25.0±5.0) ％ (attenua-tion correction, n=3). The radiochemical purity was above 99.0％ and was above 98.0％ after 6 h. The product was colorless transparent solution with pH value of 7.0-7.5, and the specific activity was (410.0± 11.0) MBq/ml and the radioactive nuclear purity was above 99.0％. PET/CT imaging in the patient showed that 18 F-PSMA-1007 was highly concentrated in prostate cancer with maximum standardized uptake value ( SUVmax ) of 40.9. Conclusion Based on CFN-MPS-200 multifunction synthesis module, 18 F-PSMA-1007 can be stably synthesized with high radiochemical yield and can be concentrated in prostate cancer.

Synthesis of 18F-PSMA-1007 by one-step method and PET/CT imaging in prostate cancer / 中华核医学与分子影像杂志

Objective@#To synthesize and analyze 18F-prostate specific membrane antigen (PSMA)-1007, followed by its imaging in prostate cancer.@*Methods@#Based on one-step method, 18F-PSMA-1007 was produced by the CFN-MPS-200 automatic synthesis module and its quality analysis was conducted. 18F-PSMA-1007 PET/CT imaging was performed in a prostate cancer patient (66 years old).@*Results@#The synthesis time of 18F-PSMA-1007 was about 50 min, and the radiochemical yield was (25.0±5.0) % (attenuation correction, n=3). The radiochemical purity was above 99.0% and was above 98.0% after 6 h. The product was colorless transparent solution with pH value of 7.0-7.5, and the specific activity was (410.0±11.0) MBq/ml and the radioactive nuclear purity was above 99.0%. PET/CT imaging in the patient showed that 18F-PSMA-1007 was highly concentrated in prostate cancer with maximum standardized uptake value (SUVmax) of 40.9.@*Conclusion@#Based on CFN-MPS-200 multifunction synthesis module, 18F-PSMA-1007 can be stably synthesized with high radiochemical yield and can be concentrated in prostate cancer.

177Lu-PSMA-I&T automated radiolabeling and preclinical prostate cancer targeting research / 中华核医学与分子影像杂志

Objective@#To synthesis 177Lu-prostate specific membrane antigen (PSMA)-I&T with automated module, evaluate the biodistribution and pharmacokinetics in mice and study the targeting property in human prostate cancer cell line LNCaP Clone FGC.@*Methods@#The iQS-TS automated module was applied in labeling 177Lu-PSMA-I&T. Radiochemical purity and stability were determined with high performance liquid chromatography (HPLC). The biodistribution was observed in normal ICR mice and U-SPECT/CT imaging was performed in LNCaP Clone FGC tumor-bearing mice. Independent-sample t test was used to analyze the data.@*Results@#177Lu-PSMA-I&T was stable in vitro and in vivo, with the radiolabeled yield of (91.5±4.9)% and radiochemical purity >99%. The half maximal inhibitory concentration (IC50) of 177Lu-PSMA-I&T binding to LNCaP Clone FGC cells was (26.74±3.53) nmol/L. The uptake of 177Lu-PSMA-I&T by LNCaP Clone FGC cells increased with time and significantly decreased after the inhibitor addition (t values: 4.301-27.483, all P<0.05). 177Lu-PSMA-I&T was cleared from blood rapidly and predominantly excreted by kidneys. Significant radioactive uptake was observed in tumors with a long retention time.@*Conclusion@#177Lu-PSMA-I&T can be produced in a convenient and efficient procedure using iQS-TS automated module, with good biological properties and excellent affinity and targeting property towards prostate cancer cells, which making it a potential radiopharmaceutical for prostate cancer therapy.

Research progress on antibacterial flavonoids / 国际生物医学工程杂志

Bacterial resistance is an increasingly serious problem.Therefore,it is necessary to find new antibacterial drugs.Flavonoids are a class of polyphenolic chemicals with low molecular weight,which exhibit many beneficial properties for human health by the interaction of cellular targets,such as the key cell signaling pathways.Flavonoids have been extensively studied as one of the important sources of antimicrobial compounds.At present,antibacterial flavonoids can be divided into two categories.One is the natural,extracted from the plant or microbial secondary metabolites.The other is the product of chemical synthesis,i.e.the derivatives of flavonoids or chalcone.In this paper,the progress of antibacterial flavonoids by natural extraction and chemical synthesis were summarized.

Research progress on antibacterial flavonoids / 国际生物医学工程杂志

Bacterial resistance is an increasingly serious problem.Therefore,it is necessary to find new antibacterial drugs.Flavonoids are a class of polyphenolic chemicals with low molecular weight,which exhibit many beneficial properties for human health by the interaction of cellular targets,such as the key cell signaling pathways.Flavonoids have been extensively studied as one of the important sources of antimicrobial compounds.At present,antibacterial flavonoids can be divided into two categories.One is the natural,extracted from the plant or microbial secondary metabolites.The other is the product of chemical synthesis,i.e.the derivatives of flavonoids or chalcone.In this paper,the progress of antibacterial flavonoids by natural extraction and chemical synthesis were summarized.

Diseño de péptidos basado en la secuencia análoga al represor negativo icaR de Staphylococcus sp / Design of peptides based on similar sequence of negative repressor icaR of Staphylococcus sp / Desenho de peptídeos com base na sequência similar ao repressor negativo icaR dos Staphylococcus sp

La biopelícula como un mecanismo de virulencia en Staphylococcus involucrada en infecciones intrahospitalarias es regulada por un represor negativo icaR, responsable de la transcripción completa del operón icaADBC. La búsqueda de dominios funcionales por modulación computacional de icaR permitió hallar las secuencias peptídicas con actividad biológica análoga a la proteína icaR. Mediante biología computacional se diseñaron péptidos empleando el programa de predicción AntiBP (http://www.imtech.res.in/raghava/antibp/); la síntesis química se hizo por Nα-Fmoc y se caracterizaron y purificaron tres moléculas por RP-HPLC y MALDI-TOF. Se evaluó su seguridad biológica mediante ensayo de actividad citotóxica realizada sobre macrófagos murinos de la línea J774 y la actividad hemolítica se determinó mediante el uso de glóbulos rojos. Los tres péptidos caracterizados IR1, IR2 e IR3, presentaron estructura secundaria predominantemente alfa helicoidal, alto grado de pureza y alto score antimicrobiano; además, mostraron baja toxicidad, evidenciada por la actividad citotóxica y hemolítica en las concentraciones ensayadas y en comparación con los controles usados, que permitiría su potencial uso como moléculas candidatas o principios activos con actividad análoga al represor nativo icaR, frente a la biopelícula de los Staphylococcus sp.

Staphylococcus sp. biofilm, formed as a mechanism of virulence that is involved in hospital acquired infections, is regulated by a negative repressor icaR, which is responsible for the full transcription of the operon icaADBC. This study, through functional commands by computational modulation of icaR, allowed to find peptide sequences with similar biological activity to the icaR protein. Peptides were designed by means of computational biology using the prediction program AntiBP (http://www.imtech.res.in/raghava/antibp/). The chemical synthesis of peptides was performed by Nα-Fmoc. The purification and characterization of three molecules were carried out using RP-HPLC and MALDI-TOF. Biological safety of peptides was evaluated by tests of cytotoxic activity on murine macrophage cells line J774, and their hemolytic activity was determined by using red cells. The three characterized peptides IR1, IR2 and IR3 presented a predominantly secondary alpha helical structure with a high degree of purity and high antimicrobial scores. In addition, the peptides exhibited low toxicity, proved by their low cytotoxic and hemolytic activity in the tested concentrations and in comparison to the standards used. These results allow the potential use of these peptides as candidate molecules or active principles with similar activity to the native repressor icaR against the Staphylococcus biofilm.

O biofilme formado como um mecanismo de virulência em Staphylococcus sp., que está envolvido com infecções intra-hospitalares, é regulado por um repressor negativo icaR, o qual é responsável pela plena transcrição do operão icaADBC. Por tanto, o presente estudo, avaliando a segurança biológica de moléculas, concebeu peptídeos antibiofilme semelhantes ao repressor icaR. Por meio da biologia computacional foram concebidos peptídeos usando o programa de predição AntiBP (http://www.imtech.res.in/raghava/antibp/) para identificar as sequências com uma atividade biologicamente similar à da proteína icaR. A Síntese química dos peptídeos se fez pelo Nα-Fmoc e foram caracterizadas e purificadas três moléculas por RP-HPLC e MALDI-TOF. O ensaio de atividade citotóxica foi realizado nos macrófagos murinos da linha J774 e a atividade hemolítica foi determinada por meio do uso de glóbulos vermelhos. Foram caraterizados três peptídeos IR1, IR2 e IR3, além de mostrarem uma estrutura secundaria predominantemente alfa helicoidal, com alto grau de pureza, alto score antimicrobiano e baixa toxicidade, estes podem ser postulados como moléculas candidatas ou princípios ativos com uma atividade similar ao repressor nativo icaR frente ao biofilme dos Staphylococcus sp.

Synthesis and preliminary evaluation of 18F-AIF-NOTA-G-TMTP1 for PET imaging on nude mice bearing high-metastatic potential hepatoma cells / 中华核医学与分子影像杂志

Objective To synthesize 18F-AlF-NOTA-G-TMTP1 and evaluate its potential for PET imaging on nude mice bearing high-metastatic potential hepatoma cells.Methods NOTA-G-TMTP1 was synthesized by the standard Fmoc-solid phase synthetic protocols and radiolabeled with 18F using NOTA-AlF chelation method.The nude mice models bearing low-metastatic potential HCC97L and high-metastatic potential HCCLM3 xenografts were established separately.The tumor-targeting characteristics of 18F-AlF-NOTA-G-TMTP1 were assessed by microPET/CT and biodistribution assay.Results NOTA-G-TMTP1 was labeled with 18F in one step with (25±6)％ labeling yield (n=5).The radiochemical purity of 18F-AlF-NOTA-G-TMTP1 was more than 95％ with a specific activity more than 11.1 GBq/μmol.The octanol/water partition coefficient (logP) for 18F-AlF-NOTA-G-TMTP1 was-3.166±0.022.The tumor to muscle ratios were 1.8± 0.4 and 4.7±0.2 at 35 min post injection for HCC97L and HCCLM3,respectively.The uptake of 18F-AlF-NOTA-G-TMTP1 in HCCLM3 tumor was inhibited (61.4％) by unlabeled G-TMTP1.Conclusion 18F-AlF-NOTA-G-TMTP1 has been successfully synthesized.It shows specific uptake by tumor induced by the high-metastatic potential hepatoma cells.

Automated synthesis and quality analysis of 18F-FMISO based on CFN-MPS-100 module / 中华核医学与分子影像杂志

Objective To synthesize 18F-FMISO and analyze the quality of the product.Methods 1-(2'-nitro-l'-imidazolyl)-2-O-tetrahydropyranyl-O-trluendulfonylpropanediol (NITIT) was taken as the precursor and simple one pot method was used.CFN-MPS-100 fluorine multifunction radiopharmaceutical chemical synthesis module was adopted to complete the radioactive fluorination reaction in a closed flat flask,and the crude product was purified by semi-preparative HPLC,the solvent was removed by rotary evaporation.Then 15 ml saline was added into the product to get 18F-FMISO injection.Radio-HPLC and radio-TLC were applied for quality control.Results 18F-FMISO was obtained in 60 min with the radiochemical yield of (32±5.0)％ (no decay corrected,n=25).The radiochemical purity was above 99.0％ and still above 98.5％ after 6 h.The radioactive concentration was above 1.11 × 1012 Bq/L.The product was colorless solution,with pH value of 7.0.The radioactive nuclear purity was more than 99％.The K222 was less than 25 μg/ml.Conclusion 18 F-FMISO could be synthesized with automatic synthesis method based on the CFN-MPS-100 fluorine multifunction module.The labeling rate,stability and chemical purity are high.