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1.
J Chem Phys ; 151(12): 125102, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31575191

RESUMO

We present an analytical model for the role of hydrogen bonding on the spin-orbit coupling of a model DNA molecule. Here, we analyze in detail the electric fields due to the polarization of the hydrogen bond on the DNA base pairs and derive, within a tight binding analytical band folding approach, an intrinsic Rashba coupling which should dictate the order of the spin active effects in the chiral-induced spin selectivity effect. The coupling found is ten times larger than the intrinsic coupling estimated previously and points out to the predominant role of hydrogen bonding in addition to chirality in the case of biological molecules. We expect similar dominant effects in oligopeptides, where the chiral structure is supported by hydrogen-bonding and bears on orbital carrying transport electrons.


Assuntos
DNA/química , Modelos Químicos , Transporte de Elétrons , Ligações de Hidrogênio , Oligopeptídeos/química
2.
Chem Pharm Bull (Tokyo) ; 67(9): 897-903, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474726

RESUMO

The word "theranostics," a portmanteau word made by combining "therapeutics" and "diagnostics," refers to a personalized medicine concept. Recently, the word, "radiotheranostics," has also been used in nuclear medicine as a term that refer to the use of radioisotopes for combined imaging and therapy. For radiotheranostics, a diagnostic probe and a corresponding therapeutic probe can be prepared by introducing diagnostic and therapeutic radioisotopes into the same precursor. These diagnostic and therapeutic probes can be designed to show equivalent pharmacokinetics, which is important for radiotheranostics. As imaging can predict the absorbed radiation dose and thus the therapeutic and side effects, radiotheranostics can help achieve the goal of personalized medicine. In this review, I discuss the use of radiolabeled probes targeting bone metastases, sigma-1 receptor, and αVß3 integrin for radiotheranostics.


Assuntos
Neoplasias Ósseas/diagnóstico , Compostos Radiofarmacêuticos/química , Animais , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/radioterapia , Meios de Contraste/química , Meios de Contraste/metabolismo , Humanos , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Oligopeptídeos/uso terapêutico , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/uso terapêutico , Receptores sigma/química , Receptores sigma/metabolismo , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Distribuição Tecidual
3.
Chem Pharm Bull (Tokyo) ; 67(9): 977-984, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474737

RESUMO

Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2, EM-1), an endogenous µ-opioid receptor ligand with strong antinociceptive activity, is not in clinical use because of its limited metabolic stability and membrane permeability. In this study, we develop a short-peptide self-delivery system for brain targets with the capability to deliver EM-1 without vehicle. Two amphiphilic EM-1 derivatives, C18-SS-EM1 and C18-CONH-EM1, were synthesized by attaching a stearyl moiety to EM-1 via a disulfide and amide bond, respectively. The amphiphilicity of EM-1 derivatives enabled self-assembling into nanoparticles for brain delivery. The study assessed morphology, circular dichroism, and metabolic stability of the formulations, as well as their pharmacodynamics and in vivo distribution, directly monitored by near-IR fluorescence imaging in mouse brains. In aqueous solution, the C18-SS-EM1 derivative self-assembled into spherical nanostructures with a diameter of 10-20 nm. Near-IR fluorescence analysis visualized the accumulation of the peptides in the brain. Importantly, the analgesic effect of C18-SS-EM1 nanoparticles was significantly stronger as compared to that of unmodified EM-1 or C18-CONH-EM1 nanoparticles. An in vitro release study demonstrated that self-assembled C18-SS-EM1 nanoparticles possessed reduction-responsive behavior. In summary, self-assembling C18-SS-EM1 nanoparticles, which integrate the advantages of lipidization, nanoscale characteristics and, labile disulfide bonds, represent a promising strategy for brain delivery of short peptides.


Assuntos
Encéfalo/metabolismo , Nanomedicina , Oligopeptídeos/farmacocinética , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/diagnóstico por imagem , Dicroísmo Circular , Portadores de Fármacos/química , Meia-Vida , Masculino , Camundongos , Nanopartículas/química , Oligopeptídeos/sangue , Oligopeptídeos/química , Espectroscopia de Luz Próxima ao Infravermelho
4.
Int J Nanomedicine ; 14: 4931-4947, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371941

RESUMO

Background: Phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), is a promising noninvasive strategy in the treatment of cancers due to its highly localized specificity to tumors and minimal side effects to normal tissues. However, single phototherapy often causes tumor recurrence which hinders its clinical applications. Therefore, developing a NIR-guided dendritic nanoplatform for improving the phototherapy effect and reducing the recurrence of tumors by synergistic chemotherapy and phototherapy is essential. Methods: A fluorescent targeting ligand, insisting of ICG derivative cypate and a tumor penetration peptide iRGD (CRGDKGPDC), was covalently combined with PAMAM dendrimer to prepare a single agent-based dendritic theranostic nanoplatform iRGD-cypate-PAMAM-DTX (RCPD). Results: Compared with free cypate, the resulted RCPD could generate enhanced singlet oxygen species while maintaining its fluorescence intensity and heat generation ability when subjected to NIR irradiation. Furthermore, our in vitro and in vivo therapeutic studies demonstrated that compared with phototherapy or chemotherapy alone, the combinatorial chemo-photo treatment of RCPD with the local exposure of NIR light can significantly improve anti-tumor efficiency and reduce the risk of recurrence of tumors. Conclusion: The multifunctional theranostic platform (RCPD) could be used as a promising method for NIR fluorescence image-guided combinatorial treatment of tumor cancers.


Assuntos
Antineoplásicos/farmacologia , Dendrímeros/química , Raios Infravermelhos , Nanopartículas/química , Fototerapia , Animais , Proliferação de Células/efeitos dos fármacos , Terapia Combinada , Docetaxel/farmacologia , Endocitose/efeitos dos fármacos , Fluorescência , Células Hep G2 , Temperatura Alta , Humanos , Indóis/farmacologia , Camundongos Nus , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Oligopeptídeos/química , Fotoquimioterapia , Propionatos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Nanomedicina Teranóstica
5.
Eur J Med Chem ; 179: 527-536, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31276897

RESUMO

New analogs of the endogenous opioid agonist endomorphin-2 (EM-2, H-Tyr-Pro-Phe-Phe-NH2) have been obtained by introducing modified tyrosines at the position 1 of the sequence. For all analogs, the cis/trans conformation ratio about the tyramine-Pro amide bond, lipophilicity, receptor affinities, and functional activities, have been determined. Among the novel derivatives, [Dmt(3'-Cl)]1EM-2 (4) stood out for its subnanomolar µ-opioid receptor affinity and potent agonist activity, superior to that of the parent peptide EM-2. Hybrid quantum mechanics/molecular mechanics docking computations supported the cis tyramine-Pro bioactive conformation, and allowed us to analyze the contribution of the substituents of the "message" tyramine to binding, highlighting the role of halogen-bonding in the higher receptor affinity of peptide 4.


Assuntos
Analgésicos Opioides/farmacologia , Teoria da Densidade Funcional , Oligopeptídeos/farmacologia , Receptores Opioides/agonistas , Tirosina/farmacologia , Analgésicos Opioides/síntese química , Analgésicos Opioides/química , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Humanos , Modelos Moleculares , Conformação Molecular , Oligopeptídeos/síntese química , Oligopeptídeos/química , Relação Estrutura-Atividade , Tirosina/química
6.
Adv Exp Med Biol ; 1140: 237-250, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347051

RESUMO

Covalent modification of proteins is extensively used in research and industry for biosensing, medical diagnostics, targeted drug delivery, and many other practical applications. The conventional method for production of protein conjugates has changed little in the last 20 years mostly relying on reactions of side chains of cysteine and lysine residues. Due to the presence of large numbers of similar reactive amino acid residues in proteins, common synthetic methods generally produce complex mixtures of products, which are difficult to separate. An emerging alternative technology for covalent modification of proteins involves formation of a covalent bond with a hexahistidine affinity tag present in a majority of recombinant proteins without interfering with other amino acid residues. The approach is based on formation of a ternary complex of the hexahistidine sequence with a bivalent metal cation chelated by ligand bearing an electrophilic Baylis-Hillman ester group capable of subsequent formation of a covalent bond with one of the histidine residues of the tag. The reaction proceeds under mild reaction conditions in neutral aqueous solutions under high dilutions (10-5 to 10-4 M) providing a stable covalent bond between the label and an imidazole residue in a hexahistidine tag at either C- or N-terminus. Because hexahistidine affinity tag methodology is a de-facto standard for preparation of recombinant proteins our approach can be easily implemented for selective derivatization of these proteins with fluorescent groups, alkynyl groups for "click" reactions, or biotinylation.


Assuntos
Histidina/química , Oligopeptídeos/química , Engenharia de Proteínas/métodos , Indicadores e Reagentes , Proteínas Recombinantes
7.
Molecules ; 24(13)2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31288488

RESUMO

In this study, we have compared four 68Ga-labeled peptides (three Arg-Gly-Asp (RGD) peptides and substance-P) with two 18F-tracers clinically approved for tumor imaging. We have studied in vitro and in vivo characteristics of selected radiolabeled tracers in a glioblastoma multiforme tumor model. The in vitro part of the study was mainly focused on the evaluation of radiotracers stability under various conditions. We have also determined in vivo stability of studied 68Ga-radiotracers by analysis of murine urine collected at various time points after injection. The in vivo behavior of tested 68Ga-peptides was evaluated through ex vivo biodistribution studies and PET/CT imaging. The obtained data were compared with clinically used 18F-tracers. 68Ga-RGD peptides showed better imaging properties compared to 18F-tracers, i.e., higher tumor/background ratios and no accumulation in non-target organs except for excretory organs.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Radioisótopos de Gálio/química , Glioblastoma/diagnóstico por imagem , Oligopeptídeos/química , Compostos Radiofarmacêuticos/química , Animais , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Feminino , Radioisótopos de Flúor , Glioblastoma/metabolismo , Humanos , Camundongos SCID , Transplante de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Tomografia por Emissão de Pósitrons/métodos , Distribuição Tecidual , Tomografia Computadorizada por Raios X
8.
Toxicol Lett ; 314: 27-36, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31295538

RESUMO

Some cosmetic ingredients can act as a chemical hapten to induce an immune response; therefore, evaluating the sensitizing potential of cosmetic ingredients is essential. We previously developed a novel in chemico direct peptide reactivity assay involving a spectrophotometric evaluation (Spectro-DPRA) for animal skin sensitization tests (local lymph node assay; LLNA). Based on previous research, we expanded the test materials to confirm the effectiveness of the Spectro-DPRA method for predicting the animal skin sensitization potential, and further determined the feasibility of the method for estimating the human skin sensitization potential. Spectro-DPRA showed 83.1% or 89.1% accuracy compared to a conventional LLNA or prediction based on human data, respectively, with a combination model using both a cysteine peptide and lysine peptide cut-off. To identify the effect of the lipophilicity of a chemical on predicting the skin sensitization potential, we applied our prediction model to chemicals with a Log Pow range of -1 to 4. Overall predictability was increased, and the accuracy compared to the LLNA and human data was 91.5% and 94.9%, respectively, in the combination cut-off prediction model. In conclusion, Spectro-DPRA serves as an easy, rapid, and high-throughput in chemico screening method with high accuracy to predict the human skin sensitization potential of chemicals.


Assuntos
Alternativas aos Testes com Animais/métodos , Ensaios de Triagem em Larga Escala , Oligopeptídeos/química , Testes de Irritação da Pele/métodos , Pele/efeitos dos fármacos , Animais , Cisteína , Estudos de Viabilidade , Humanos , Ensaio Local de Linfonodo , Lisina , Estrutura Molecular , Reprodutibilidade dos Testes , Medição de Risco , Pele/imunologia , Espectrofotometria , Relação Estrutura-Atividade
9.
Soft Matter ; 15(27): 5375-5379, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31259985

RESUMO

Herein, a novel photothermal agent based on polyoxometalate clusters and food-borne antioxidant peptides was exploited to overcome the inherent problems of poor photothermal stability of polyoxometalate photothermal materials, which commonly appear in the current stage of development, and the inevitable simultaneous inflammatory responses during the therapeutic process.


Assuntos
Antibacterianos/química , Antioxidantes/química , Materiais Biocompatíveis/química , Nanopartículas/química , Oligopeptídeos/química , Compostos de Tungstênio/química , Antibacterianos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Estabilidade de Medicamentos , Escherichia coli/efeitos dos fármacos , Células Hep G2 , Humanos , Hipertermia Induzida , Raios Infravermelhos , Fototerapia/métodos , Temperatura Ambiente
10.
Eur J Med Chem ; 177: 235-246, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31152989

RESUMO

Culicinin D is a 10 amino acid peptaibol containing a rare and synthetically challenging (2S,4S,6R)-AHMOD residue, that exhibits potent antiproliferative activity against MDA-MB-468 cells. An SAR study focusing on replacement of the AHMOD residue was undertaken, culminating in the revelation that a 6-hydroxy or 6-keto substituent was essential to retain potent low nanomolar antiproliferative activity.


Assuntos
Antineoplásicos/farmacologia , Oligopeptídeos/farmacologia , Peptaibols/farmacologia , Substituição de Aminoácidos , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Ácidos Decanoicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Oligopeptídeos/síntese química , Oligopeptídeos/química , Peptaibols/síntese química , Peptaibols/química , Estereoisomerismo , Relação Estrutura-Atividade
11.
Int J Nanomedicine ; 14: 3455-3468, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190803

RESUMO

Background: Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a novel tumor suppressor. However, whether LHPP is effective to melanoma has not been investigated. Gene therapy provides a new strategy for the treatment of melanoma. Currently, it suffers from the lack of safe and effective gene delivery systems. Methods: A CRGDKGPDC peptide (iRGD) modified hybrid monomethoxy poly(ethylene glycol)-poly(D,L-lactide) nanoparticle (iDPP) was prepared and complexed with a LHPP plasmid, forming an iDPP/LHPP nanocomplex. The iDPP/LHPP nanocomplex was characterized by particle size distribution, zeta potential, morphology, cytotoxicity, and transfection efficiency. The antitumor efficacy of the nanocomplex against melanoma was studied both in vitro and in vivo. Further, the potential epigenetic changes in melanoma induced by iDPP/LHPP nanocomplex were evaluated. Results: The iDPP/LHPP nanocomplex showed high transfection efficiency and low toxicity. Moreover, the nanocomplex displayed a neutral charge that can meet the requirement of intravenous injection for targeted gene therapy. In vitro and in vivo experiments indicated that the iDPP/LHPP nanocomplex significantly inhibited the melanoma growth without causing notable adverse effects. We also found that LHPP played an important role in epigenetics. It regulated the expression of genes related to the proliferation and apoptosis chiefly at the level of transcription. Conclusion: This work demonstrates that the iDPP nanoparticle-delivered LHPP gene has a potential application in melanoma therapy through regulation of the genes associated with epigenetics.


Assuntos
Pirofosfatase Inorgânica/uso terapêutico , Melanoma Experimental/tratamento farmacológico , Nanopartículas/química , Animais , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Epigênese Genética/efeitos dos fármacos , Humanos , Melanoma Experimental/patologia , Camundongos Endogâmicos C57BL , Nanopartículas/ultraestrutura , Oligopeptídeos/química , Especificidade de Órgãos/efeitos dos fármacos , Poliésteres/química , Polietilenoglicóis/química
12.
Food Chem ; 297: 124931, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31253328

RESUMO

Enzyme hydrolysis of corn gluten meal (CGM) is a promising process to prepare oligopeptides with high Fischer ratios (HFOPs). However, the relationship between Fischer ratios and enzyme hydrolysis approaches remains poorly understood. In this study, peptidomes of varying corn protein hydrolysates (CPHs) before and after activated carbon adsorption were profiled and analyzed according to sequence composition and chain length. Fischer ratios of HFOPs depended on sequences in CPHs by differing enzyme hydrolysis approaches, especially branched-chain amino acid (BCAA)-aromatic amino acid (AAA)-containing-oligopeptides. Activated carbon adsorption increased BCAA-containing-oligopeptide contents and decreased oligopeptide contents including AAAs, preferring BCAA-AAA-containing-oligopeptides with long chain length. Employing a three-enzyme hydrolysis approach, HFOPs were obtained with a yield of 49%, comprising 90% of dipeptides and tripeptides and possessing additional bioactivities. This work revealed the mechanism of HFOP production depending on the release and selective removal of oligopeptides and confirmed CGM was a promising alternative for value-added HFOP production.


Assuntos
Glutens/metabolismo , Oligopeptídeos/química , Zea mays/metabolismo , Adsorção , Aminoácidos Aromáticos/química , Aminoácidos de Cadeia Ramificada/química , Carbono/química , Cromatografia Líquida de Alta Pressão , Hidrólise , Peso Molecular , Oligopeptídeos/metabolismo , Peptídeo Hidrolases/metabolismo , Espectrometria de Massas em Tandem
14.
Food Chem ; 293: 368-377, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31151624

RESUMO

In this study, the efficiency and practical utilization feasibility of niosomal and liposomal nanovesicles loading Isoleucine-Proline-Proline (IPP) as suitable ingredients of functional beverages were evaluated. Vesicles were tailored by different preparation methods using phospholipid and non-ionic surfactants. The optimization process was performed by central composite design approach. The results of Fourier transform infrared spectroscopy demonstrated the compatibility of IPP with the vesicles. The phospholipidic nanovesicles, produced by modified ethanol injection-microchannel technique, were smaller with lower polydispersity index than non-ionic surfactant vesicles developed by the method of thin film hydration and probe sonication. However, niosomal model functional beverage exhibited more proper palatability, biological activity and physicochemical properties during long-term storage than liposomal one. Moreover, niosomes exhibited more sustained release behaviour in simulated blood fluid than liposomes. These findings are of great importance for design and development of the functional foods containing IPP.


Assuntos
Bebidas , Alimentos Fortificados , Nanoestruturas/química , Oligopeptídeos/química , Difusão Dinâmica da Luz , Manipulação de Alimentos/métodos , Armazenamento de Alimentos , Suco Gástrico/metabolismo , Humanos , Lipossomos/química , Microscopia Eletrônica de Transmissão , Oligopeptídeos/farmacocinética , Fosfolipídeos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Tensoativos/química
15.
Phys Chem Chem Phys ; 21(24): 12843-12849, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31179453

RESUMO

Methods based on fluorescence resonance energy transfer (FRET) and photo-induced electron transfer (PET) are widely used in the biological sciences, employing mostly dye-based FRET and PET pairs. While very useful and important, dye-based reporters are not always applicable without concern, for example, in cases where the fluorophore size needs to be minimized. Therefore, development and characterization of smaller, ideally amino acid-based PET and FRET pairs will expand the biological spectroscopy toolbox to enable new applications. Herein, we show that, depending on the excitation wavelength, tryptophan and 4-cyanotrptophan can interact with each other via the mechanism of either energy or electron transfer, hence constituting a dual FRET and PET pair. The biological utility of this amino acid pair is further demonstrated by applying it to study the end-to-end collision rate of a short peptide, the mode of interaction between a ligand and BSA, and the activity of a protease.


Assuntos
Triptofano/análogos & derivados , Triptofano/química , Transporte de Elétrons , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes/química , Ligantes , Oligopeptídeos/química , Ligação Proteica , Soroalbumina Bovina/química , Espectrometria de Fluorescência , Tripsina/química
16.
Phys Chem Chem Phys ; 21(24): 13207-13214, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31179459

RESUMO

The local valence orbital structure of solid glycine, diglycine, and triglycine is studied using soft X-ray emission spectroscopy (XES), resonant inelastic soft X-ray scattering (RIXS) maps, and spectra calculations based on density-functional theory. Using a building block approach, the contributions of the different functional groups of the peptides are separated. Cuts through the RIXS maps furthermore allow monitoring selective excitations of the amino and peptide functional units, leading to a modification of the currently established assignment of spectral contributions. The results thus paint a new-and-improved picture of the peptide bond, enhance the understanding of larger molecules with peptide bonds, and simplify the investigation of such molecules in aqueous environment.


Assuntos
Modelos Químicos , Peptídeos/química , Difusão Dinâmica da Luz , Elétrons , Glicina/química , Glicilglicina/química , Oligopeptídeos/química , Teoria Quântica , Água/química , Difração de Raios X
17.
Int J Nanomedicine ; 14: 4071-4090, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239668

RESUMO

Background: Chemotherapy for non-small-cell lung cancer (NSCLC) still leads to unsatisfactory clinical prognosis because of poor active targeting and tumor metastasis. Purpose: The objective of this study was to construct a kind of PFV peptide modified targeted daunorubicin and dioscin codelivery liposomes, which could enhance tumor targeting and inhibit tumor cell metastasis. Methods and results: Targeted daunorubicin and dioscin codelivery liposomes were prepared by film dispersion and the ammonium sulfate gradient method. With the ideal physicochemical properties, targeted daunorubicin and dioscin codelivery liposomes exhibited enhanced cellular uptake and showed strong cytotoxicity to tumor cells. The encapsulation of dioscin increased the inhibitory effects of daunorubicin on A549 cells, vasculogenic mimicry (VM) channels and tumor metastasis. The enhanced antimetastatic mechanism of the targeted liposomes was attributed to the downregulation of matrix metalloproteinase-2 (MMP-2), vascular endothelial cadherin (VE-Cad), transforming growth factor-ß1 (TGF-ß1) and hypoxia inducible factor-1α (HIF-1α). Meanwhile, the targeted daunorubicin and dioscin codelivery liposomes exhibited significant antitumor effects in tumor-bearing mice. H&E staining, immunohistochemistry with Ki-67 and TUNEL assay also showed the promoted antitumor activity of the targeted liposomes. Conclusion: Targeted daunorubicin and dioscin codelivery liposomes may provide an effective strategy for the treatment of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Daunorrubicina/uso terapêutico , Diosgenina/análogos & derivados , Sistemas de Liberação de Medicamentos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Oligopeptídeos/química , Células A549 , Animais , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/irrigação sanguínea , Movimento Celular/efeitos dos fármacos , Daunorrubicina/administração & dosagem , Daunorrubicina/farmacologia , Diosgenina/administração & dosagem , Diosgenina/farmacologia , Diosgenina/uso terapêutico , Feminino , Humanos , Lipossomos , Neoplasias Pulmonares/irrigação sanguínea , Metaloproteinase 2 da Matriz , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , Tamanho da Partícula , Eletricidade Estática , Cicatrização/efeitos dos fármacos
18.
Talanta ; 201: 450-454, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31122448

RESUMO

A novel aggregation-induced emission (AIE) probe comprised of a hydrophilic protein kinase specific peptide and a hydrophobic tetraphenylethene (TPE) unit was synthesized through click reaction. The prepared TPE-peptide probe could be completely degraded by carboxypeptidase Y (CPY) to release hydrophobic TPE part, which aggregated in buffer solution and showed strong TPE emission. In the presence of casein kinase (CKII), the phosphorylation of peptide prevented the complete degradation by CPY producing the nonemissive probe. Thus, the developed probe can be used to detect CKII homogeneously and conveniently. This detection process can be finished within 1.5 h with high sensitivity (0.05 mU/µL) and good selectivity. The developed method can also be used to screen protein kinase inhibitor even in a complex biological system.


Assuntos
Técnicas Biossensoriais/métodos , Caseína Quinase II/análise , Ensaios Enzimáticos/métodos , Espectrometria de Fluorescência/métodos , Compostos de Benzilideno/síntese química , Compostos de Benzilideno/química , Caseína Quinase II/química , Catepsina A/química , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Células HeLa , Humanos , Oligopeptídeos/síntese química , Oligopeptídeos/química , Fosforilação , Inibidores de Proteínas Quinases/química , Proteólise , Triazóis/química
19.
Phys Chem Chem Phys ; 21(22): 11916-11923, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31125036

RESUMO

Peptide structural transformation and aggregation is associated with a large number of outsider aetiology diseases, and it is intrinsically linked to amyloid peptide aggregation. Diphenylalanine self-assembled structures are used as robust minimalist beta amyloids not only to elucidate protein aggregation but also to generate hydrogels. Herein, we employed a neutral model peptide Ac-Phe-Phe-Cys-NH2 (Ac-FFC-NH2) to elucidate the role of intermolecular disulfide bonds in protein fibrillation. The Ac-FFC-NH2 peptide initially self-assembles into nanospheres that evolve to amyloid type fibrils under mild oxidative conditions. Incubation of the peptide in the presence of the chemical reduction agent TCEP inhibits the formation of the fibrils, detecting only spherical nanostructures with no secondary structure. Importantly, we triggered the transformation of the preformed linear straight amyloid fibrils to non-fibrillar structures by TCEP treatment. Under this condition, the amyloid bundles are transformed into rings, which evolve to a new spherical microstructure. We showed that the chemical reduction of intermolecular S-S in internal amyloid sequences might favour the off-path intermediates of amyloid fibril growth, even when the fibrils are formed. Our findings demonstrated that in internal amyloid sequences, the formation of intermolecular S-S promotes the formation of amyloid type fibrils; meanwhile, its reduction stabilises non-fibrillar structures. Altogether, this work provides fundamental understanding at the molecular and supramolecular level, thus facilitating the rational design of therapeutic tools for protein aggregation diseases.


Assuntos
Amiloide/química , Dissulfetos/química , Oligopeptídeos/química , Oligopeptídeos/síntese química , Oxirredução , Multimerização Proteica
20.
J Chem Phys ; 150(17): 174705, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31067872

RESUMO

Motivated by a recent experiment [C. Guo et al., Proc. Natl. Acad. Sci. U. S. A. 113, 10785 (2016)], we carry out a theoretical study of electron transport through peptide-based single-molecule junctions. We analyze the pristine hepta-alanine and its functionalizations with a single tryptophan unit, which is placed in three different locations along the backbone. Contrary to expectations from the experiment on self-assembled monolayers, we find that insertion of tryptophan does not raise the electrical conductance and that the resulting peptides instead remain insulating in the framework of a coherent transport picture. The poor performance of these molecules as conductors can be ascribed to the strongly off-resonant transport and low electrode-molecule coupling of the frontier orbitals. Although the introduction of tryptophan increases the energy of the highest occupied molecular orbital (HOMO) of the peptides in the gas phase, the new HOMO states are localized on the tryptophan unit and therefore essentially do not contribute to coherent charge transport.


Assuntos
Oligopeptídeos/química , Triptofano/química , Teoria da Densidade Funcional , Condutividade Elétrica , Modelos Químicos , Estrutura Molecular
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