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1.
Chem Commun (Camb) ; 55(69): 10192-10213, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31411602

RESUMO

Light is unsurpassed in its ability to modulate biological interactions. Since their discovery, chemists have been fascinated by photosensitive molecules capable of switching between isomeric forms, known as photoswitches. Photoswitchable peptides have been recognized for many years; however, their functional implementation in biological systems has only recently been achieved. Peptides are now acknowledged as excellent protein-protein interaction modulators and have been important in the emergence of photopharmacology. In this review, we briefly explain the different classes of photoswitches and summarize structural studies when they are incorporated into peptides. Importantly, we provide a detailed overview of the rapidly increasing number of examples, where biological modulation is driven by the structural changes. Furthermore, we discuss some of the remaining challenges faced in this field. These exciting proof-of-principle studies highlight the tremendous potential of photocontrollable peptides as optochemical tools for chemical biology and biomedicine.


Assuntos
Descoberta de Drogas , Peptídeos/química , Peptídeos/farmacologia , Sequência de Aminoácidos , Animais , Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Morte Celular/efeitos dos fármacos , Descoberta de Drogas/métodos , Humanos , Isomerismo , Luz , Modelos Moleculares , Ácidos Nucleicos/metabolismo , Peptídeos/metabolismo , Processos Fotoquímicos , Mapas de Interação de Proteínas/efeitos dos fármacos
2.
J Agric Food Chem ; 67(33): 9241-9253, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31369258

RESUMO

Antiviral compounds targeting viral replicative processes have been studied as an alternative for the control of begomoviruses. Previously, we have reported that the peptide AmPep1 has strong affinity binding to the replication origin sequence of tomato yellow leaf curl virus (TYLCV). In this study, we describe the mechanism of action of this peptide as a novel alternative for control of plant-infecting DNA viruses. When AmPep1 was applied exogenously to tomato and Nicotiana benthamiana plants infected with TYLCV, a decrease in the synthesis of the two viral DNA strands (CS and VS) was observed, with a consequent delay in the development of disease progress in treated plants. The chemical mechanism of action of AmPep1 was deduced using Raman spectroscopy and molecular modeling showing the formation of chemical interactions such as H bonds and electrostatic interactions and the formation of π-π interactions between both biomolecules contributing to tampering with the viral replication.


Assuntos
Amaranthus/química , Antivirais/química , Antivirais/farmacologia , Begomovirus/efeitos dos fármacos , Peptídeos/química , Peptídeos/farmacologia , RNA Viral/química , Replicação Viral/efeitos dos fármacos , Begomovirus/química , Begomovirus/genética , Begomovirus/fisiologia , Sequências Repetidas Invertidas/efeitos dos fármacos , Lycopersicon esculentum/virologia , Doenças das Plantas/virologia , Proteínas de Plantas/química , RNA Viral/genética , Tabaco/virologia
3.
World J Microbiol Biotechnol ; 35(9): 133, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31432254

RESUMO

There is a significant increase in the discovery of new antimicrobial compounds in recent past to combat drug resistant pathogens. Members of the genus Bacillus and related genera have been screened extensively due to their ability to produce wide range of antimicrobial compounds. In this study, we have isolated and characterized a new antimicrobial peptide from a marine bacterium identified as Virgibacillus species. The low molecular mass and stability of the antimicrobial substance pointed towards the bacteriocinogenic nature of the compound. The RAST analysis of genome sequence showed presence of a putative bacteriocin biosynthetic cluster containing genes necessary for synthesis of a lanthipeptide. Translated amino acid sequence of mature C-terminal propeptide showed identity with salivaricin A (52.2%) and lacticin A (33.3%). Accordingly, the mass (2417 Da) obtained by MALDI analysis was in agreement with posttranslational modifications of the leader peptide to yield three methyl lanthionine rings and a disulfide bond between two free cysteine residues. The lanthipeptide was named as virgicin, which selectively inhibited the growth of Gram-positive bacteria and biofilm formation by Enterococcus faecalis. Inhibition of biofilm formation by E. faecalis was also observed in in vitro model experiments using hydroxyapatite discs. Thus, virgicin appears to be a promising new bacteriocin to control oral biofilm formation by selective pathogens.


Assuntos
Bacteriocinas/isolamento & purificação , Bacteriocinas/farmacologia , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/crescimento & desenvolvimento , Peptídeos/isolamento & purificação , Peptídeos/farmacologia , Virgibacillus/metabolismo , Bacteriocinas/química , Bacteriocinas/genética , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Vias Biossintéticas/genética , Genoma Bacteriano , Peso Molecular , Família Multigênica , Peptídeos/química , Peptídeos/genética , Água do Mar/microbiologia , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Virgibacillus/classificação , Virgibacillus/isolamento & purificação
4.
Chem Commun (Camb) ; 55(68): 10142-10145, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31389424

RESUMO

Hydrogen sulfide, an endogenous signalling molecule, is central to several pathophysiological processes in mammalian systems. It scavenges reactive oxygen species and is known to ameliorate dopaminergic neuronal degeneration in neurotoxin-induced Parkinson's disease models. The rapid volatilization of H2S from spontaneously releasing sulfide salts being a challenge, we describe peptide conjugates which exhibit tris(2-carboxyethyl)phosphine mediated "slow and sustained" H2S release. These conjugates reduced hydrogen peroxide-induced oxidative stress and significantly increased dopamine levels in transgenic C. elegans.


Assuntos
Dopamina/metabolismo , Sulfeto de Hidrogênio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/farmacologia , Tionas/farmacologia , Tiofenos/farmacologia , Animais , Animais Geneticamente Modificados , Anti-Inflamatórios/metabolismo , Antioxidantes/metabolismo , Caenorhabditis elegans/genética , Liberação Controlada de Fármacos , Oxirredução , Peptídeos/síntese química , Peptídeos/química , Fosfinas/química , Pró-Fármacos/síntese química , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Tionas/síntese química , Tionas/química , Tiofenos/síntese química , Tiofenos/química , alfa-Sinucleína/genética
5.
J Agric Food Chem ; 67(38): 10604-10613, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31466448

RESUMO

The aim of this study was to investigate the dipeptidyl peptidase-IV (DPP-IV) inhibition and metabolic stability of a casein-derived peptide Val-Pro-Tyr-Pro-Gln (VPYPQ) and its fragments as well as their release from casein following hydrolysis. Results showed that VPYPQ was the most potent DPP-IV inhibitory peptide among them with an IC50 value of 41.45 µM. This might be due to its two internal Pro residues at positions 2 and 4. Moreover, VPYPQ was resistant to hydrolysis by gastrointestinal enzymes and was relatively more stable to hydrolysis by DPP-IV and peptidases in plasma compared with its fragments. Additionally, oral administration of VPYPQ at a dose of 90 µmol/kg body weight could reduce the postprandial blood glucose levels in mice. More importantly, VPYPQ could be released efficiently from casein following hydrolysis by a combination of papain and in vitro digestion, reaching up to 3211.15 µg/g. Therefore, VPYPQ was a promising casein-derived DPP-IV inhibitor.


Assuntos
Caseínas/química , Preparações de Ação Retardada/química , Inibidores da Dipeptidil Peptidase IV/química , Peptídeos/química , Animais , Biocatálise , Glicemia/metabolismo , Preparações de Ação Retardada/administração & dosagem , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Dipeptidil Peptidase 4/química , Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Teste de Tolerância a Glucose , Humanos , Hidrólise , Camundongos , Peptídeo Hidrolases/química , Peptídeo Hidrolases/metabolismo , Peptídeos/administração & dosagem , Ratos , Ratos Sprague-Dawley
6.
J Cancer Res Clin Oncol ; 145(10): 2457-2468, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31463718

RESUMO

BACKGROUND: Our previous study identified a Wilms tumor-suppressing peptide (WTSP) that was upregulated in healthy children, but downregulated in children with Wilms tumor (WT). This study aimed to investigate the effect of WTSP on WT growth in vivo and in vitro. METHODS: WTSP was synthesized by solid-phase synthesis of FOMC-protected amino acids. Cell growth curve, cytotoxicity, and apoptosis of WTSP-treated human WT cell line (SK-NEP-1) were determined by cell count, Cell Counting Kit-8 assay, and flow cytometry. The expression of key proteins of four WT-associated signaling pathways was determined by real-time PCR and western blotting. The WT xenograft mouse model was established by the armpit injection of SK-NEP-1 cells. The TUNEL assay was used to detect apoptosis in mouse tumor cells. RESULTS: WTSP inhibited the proliferation of SK-NEP-1 cells in a dose- and time-dependent manner, and it arrested SK-NEP-1 cells in G2/M phase. WTSP-treated cells exhibited a low expression of PCNA and Bcl-2 and high expression of Bax. The expression of ß-catenin was markedly changed after WTSP treatment. WTSP-treated mice had significantly smaller tumors than untreated mice. CONCLUSION: Our findings indicated an anti-tumor effect of WTSP, which is correlated with Wnt/ß-catenin pathway. This newly identified peptide may exert a therapeutic effect of WT in the future.


Assuntos
Apoptose/efeitos dos fármacos , Peptídeos/farmacologia , Animais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Camundongos , Peptídeos/síntese química , Peptídeos/química , Transdução de Sinais , Tumor de Wilms/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Inorg Chem ; 58(17): 11782-11792, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31433630

RESUMO

Reproduction of the dominant vector of Zika and dengue diseases, Aedes aegypti mosquito, is controlled by an active heterodimer complex composed of the 20-hydroxyecdysone receptor (EcR) and ultraspiracle protein. Although A. aegypti EcR shares the structural and functional organization with other nuclear receptors, its C-terminus has an additional long F domain (AaFEcR). Recently, we showed that the full length AaFEcR is intrinsically disordered with the ability to specifically bind divalent metal ions. Here, we describe the details of the exhaustive structural and thermodynamic properties of Zn2+- and Cu2+-complexes with the AaFEcR domain, based on peptide models of its two putative metal binding sites (Ac-HGPHPHPHG-NH2 and Ac-QQLTPNQQQHQQQHSQLQQVHANGS-NH2). Unexpectedly, only in the presence of increasing concentrations of Cu2+ ions, the Ac-HGPHPHPHG-NH2 peptide gained a metal ion-induced poly-l-proline type II helical structure, which is unique for members of the family of nuclear receptors.


Assuntos
Aedes/efeitos dos fármacos , Antivirais/farmacologia , Cobre/farmacologia , Compostos Organometálicos/farmacologia , Peptídeos/farmacologia , Receptores de Esteroides/antagonistas & inibidores , Animais , Antivirais/química , Sítios de Ligação/efeitos dos fármacos , Cobre/química , Dengue/tratamento farmacológico , Dengue/metabolismo , Estrutura Molecular , Compostos Organometálicos/química , Peptídeos/química , Receptores de Esteroides/metabolismo , Termodinâmica , Infecção por Zika virus/tratamento farmacológico , Infecção por Zika virus/metabolismo
8.
Inorg Chem ; 58(17): 11649-11655, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31436093

RESUMO

A new mixed-valent dicopper complex [5] was generated from ligand exchange by dissolving a bis(CH3CN) precursor [3] in acetone. Introduction of a water molecule in place of an acetonitrile ligand was evidenced by base titration and the presence of a remaining coordinated CH3CN by IR, 19F NMR, and theoretical methods. The proposed structure (CH3CN-Cu-(SR)-Cu-OH2) was successfully DFT-optimized and the calculated parameters are in agreement with the experimental data. [5] has a unique temperature-dependence EPR behavior, with a localized valence from 10 to 120 K that undergoes delocalized at room temperature. The electrochemical signatures are in the line of the other aquo parent [2] and sensibly different from the rest of the series. Similar to the case of [2], [5] was finally capable of single turnover N2O reduction at room temperature. N2 was detected by GC-MS, and the redox character was confirmed by EPR and ESI-MS. Kinetic data indicate a reaction rate order close to 1 and a rate 10 times faster compared to [2]. [5] is thus the second example of that kind and highlights not only the main role of the Cu-OH2 motif, but also that the adjacent Cu-X partner (X = OTf- in [2] and CH3CN in [5]) is a new actor in the casting to establish structure/activity correlations.


Assuntos
Cobre/farmacologia , Inibidores Enzimáticos/farmacologia , Compostos Organometálicos/farmacologia , Oxirredutases/antagonistas & inibidores , Peptídeos/farmacologia , Cobre/química , Teoria da Densidade Funcional , Técnicas Eletroquímicas , Inibidores Enzimáticos/química , Estrutura Molecular , Compostos Organometálicos/química , Oxirredutases/metabolismo , Peptídeos/química
9.
Adv Exp Med Biol ; 1158: 101-117, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31452138

RESUMO

Targeted mass spectrometry in the selected or parallel reaction monitoring (SRM or PRM) mode is a widely used methodology to quantify proteins based on so-called signature or proteotypic peptides. SRM has the advantage of being able to quantify a range of proteins in a single analysis, for example, to measure the level of enzymes comprising a biochemical pathway. In this chapter, we will detail how to set up an SRM assay on the example of the mitochondrial protein succinate dehydrogenase [ubiquinone] flavoprotein subunit (mouse UniProt-code Q8K2B3). First, we will outline the in silico assay design including the choice of peptides based on a range of properties. We will further delineate different quantification strategies and introduce the reader to LC-MS assay development including the selection of the optimal peptide charge state and fragment ions as well as a discussion of the dynamic range of detection. The chapter will close with an application from the area of mitochondrial biology related to the quantification of a set of proteins isolated from mouse liver mitochondria in a study on mitochondrial respiratory flux decline in aging mouse muscle.


Assuntos
Mitocôndrias , Proteômica , Animais , Cromatografia Líquida , Camundongos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Peptídeos/química , Proteômica/instrumentação , Proteômica/métodos , Espectrometria de Massas em Tandem
10.
Phys Chem Chem Phys ; 21(33): 18219-18226, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31389931

RESUMO

The villin headpiece subdomain (HP35) is a fast-folding protein with 35 residues and its folding pathways have been extensively studied experimentally and theoretically but remain controversial. While experiments showed that HP35 might have multiple folding pathways, most theoretical studies only found one major pathway, although a few theoretical studies revealed two. Here we report our results of molecular dynamics simulations of HP35 folding by using the newest AMBER ff14SB force field and show that HP35 has a novel folding pathway in addition to the two pathways shown previously. We also study the mechanism of determining the folding pathways and found that the dynamics of Helix2 may play a special role in the folding of HP35. Our results may be helpful to understand the folding mechanism of HP35 further.


Assuntos
Proteínas dos Microfilamentos/química , Simulação de Dinâmica Molecular , Peptídeos/química , Dobramento de Proteína , Domínios Proteicos , Termodinâmica
11.
Chem Commun (Camb) ; 55(70): 10484-10487, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31414101

RESUMO

The de novo design of stapled peptide-based self-assemblies attracts vast interest, yet still remains challenging. The development of an oxidation trigger for peptide stapling and subsequent self-assembly is described here. A self-assembling sequence, Fmoc-R(RCEX)2-NH2, transformed from a random coil to an α-helical structure upon disulphide bonding of the flanking cysteine residues positioning at the i/i + 4 locations. The stapling form of this peptide enforces a conformational restraint that affords the driving force for self-assembly into nanorod/nanovesicle structures. Moreover, these assembled materials can transport siRNA into cancer cells and immediately release the cargo in a reductive environment.


Assuntos
Peptídeos/química , Microscopia de Força Atômica , Oxirredução , Conformação Proteica em alfa-Hélice
12.
Chem Pharm Bull (Tokyo) ; 67(7): 620-631, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257316

RESUMO

Natural products are still rich sources of clinically used medicines and lead compounds for them. This review summarizes chemical studies carried out by the author on natural products of microorganism origin, many of which were discovered at the Institute of Microbial Chemistry (BIKAKEN). Caprazamycin B is a liponucleoside antibiotic from which CPZEN-45, an antituberculosis agent with a unique mode of action, was developed. Intervenolin and leucinostatin A exert antiproliferative activity toward tumor cells in the presence of the corresponding stromal cells, which implies that the primary molecular targets of these molecules should be related to growth signals from normal (stromal) cells. Details of the endeavors to establish efficient synthetic routes to these compounds which accelerated structure-activity relationship studies and further evaluation of biological activity are described.


Assuntos
Anti-Infecciosos/química , Antineoplásicos/química , Produtos Biológicos/química , Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Antineoplásicos/farmacologia , Azepinas/química , Azepinas/farmacologia , Produtos Biológicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Peptídeos/química , Peptídeos/farmacologia , Relação Estrutura-Atividade
13.
J Chem Theory Comput ; 15(8): 4699-4707, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31314523

RESUMO

We present a fast implementation of the nudged elastic band (NEB) method into the particle mesh Ewald molecular dynamics module of the Amber software package for both central processing units (CPU) and graphics processing units (GPU). The accuracy of the new implementation has been validated for three cases: a conformational change of alanine dipeptide, the α-helix to ß-sheet transition in polyalanine, and a large conformational transition in the human 8-oxoguanine-DNA glycosylase with DNA complex (OGG1-DNA). Timing benchmark tests were performed on the explicitly solvated OGG1-DNA system containing ∼50 000 atoms. The GPU-optimized implementation of NEB achieves a more than two orders of magnitude speedup compared with the previous CPU implementation performed with a two-core CPU processor. The speed and scalable features of this implementation will enable NEB applications on larger and more complex systems.


Assuntos
DNA Glicosilases/química , Dipeptídeos/química , Simulação de Dinâmica Molecular , Peptídeos/química , Gráficos por Computador , DNA/química , Humanos , Conformação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Software , Fatores de Tempo
14.
J Agric Food Chem ; 67(32): 8855-8867, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31343893

RESUMO

Abalone (Haliotis discus hannai) is a precious seafood in the market. It has been reported that biological active substances derived from abalone have anti-oxidative, anti-inflammatory, anti-bacterial, and anti-thrombosis potential. However, there were few studies to assess whether they have anti-cancer potential. In this study, we evaluated the anti-metastasis and anti-pro-angiogenic factors and mechanism of action of boiled abalone byproduct peptide (BABP, EMDEAQDPSEW) in human fibrosarcoma (HT1080) cells and human umbilical vein endothelial cells (HUVECs). The results demonstrated that BABP treatment significantly lowers migration and the invasion of HT1080 cells and HUVECs. BABP inhibits phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase (MMP) expression and activity by blocking mitogen-activated protein kinases (MAPKs) and NF-κB signaling and hypoxia-induced vascular endothelial growth factor (VEGF) secretion and hypoxia inducible factor (HIF)-1α accumulation through suppressing the AKT/mTOR signal pathway. BABP treatment inhibits VEGF-induced VEGFR-2 expression and tube formation in HUVECs. The effect of BABP on anti-metastatic and anti-vascular activity in HT1080 cells and HUVECs revealed that BABP may be a potential pharmacophore for tumor therapy in the future.


Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos/farmacologia , Gastrópodes/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Peptídeos/farmacologia , Resíduos/análise , Inibidores da Angiogênese/química , Inibidores da Angiogênese/isolamento & purificação , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Metástase Neoplásica , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/fisiopatologia , Peptídeos/química , Peptídeos/isolamento & purificação , Frutos do Mar/análise , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
15.
Biomed Khim ; 65(3): 180-201, 2019 Apr.
Artigo em Russo | MEDLINE | ID: mdl-31258142

RESUMO

New data on peptide drugs have been summarized; their high stability is due to both the introduction of Pro-Gly-Pro in various amino acid sequences and the modification of the glyproline fragment itself. Pro-Gly-Pro-Leu, ACTH(6-9)Pro-Gly-Pro, 5-oxo-Pro-Arg-Pro and 5-oxo-Pro-His-Pro-NH2 were used as proline-containing peptides. Tritiated peptides were obtained: Pro-Gly-Pro-Leu with specific radioactivity of 135 Ci/mmol, ACTH(6-9)Pro-Gly-Pro - 26 Ci/mmol, 5-oxo-Pro-Arg-Pro - 60 Ci/mmol and 5-oxo-Pro-His-Pro-NH2 - 75 Ci/mmol. The concentration of Pro-Gly-Pro-Leu, ACTH(6-9)Pro-Gly-Pro, 5-oxo-Pro-Arg-Pro and 5-oxo-Pro-His-Pro-NH2 in the blood was found to be about 200 times more than in the brain for intranasal administration, and in average 600 times more for intravenous administration. The stability of proline-containing peptides in vitro experiments was determined using different commercially available peptidases (leucine aminopeptidases, dipeptidases, carboxypeptidases B and Y), and using nasal mucus, microsomal fraction of the rat brain (IMPC) and rat blood plasma. During peptidase hydrolysis of Pro-Gly-Pro-Leu, the main metabolites were Gly-Pro-Leu, Pro-Gly-Pro, Gly-Pro and Pro-Gly. For ACTH(6-9)Pro-Gly-Pro, the main metabolites were Phe-Arg-Trp-Pro-Gly-Pro and Trp-Pro-Gly-Pro. In peptidase hydrolysis of 5-oxo-Pro-His-Pro-NH2, the major metabolite was 5-oxo-Pro-His-Pro. It was shown that with different methods of peptides administration the composition of the metabolites formed is different. Based on the data obtained, resistance to enzymatic cleavage of peptides and their metabolic pathways were evaluated. Thus, these new data have shown that the above approaches can be used to prolong the action of glyprolines in living objects. In this case, the degradation of proline-containing peptides occurs mainly not due to the action of proteases, but due to other ways of degradation. In general, the data presented in the review indicate the promise of intranasal way of introducing biologically active peptides into the brain of living organisms.


Assuntos
Peptídeos/química , Prolina/química , Sequência de Aminoácidos , Animais , Peptídeo Hidrolases/química , Estabilidade Proteica , Ratos
16.
Chem Commun (Camb) ; 55(61): 8959-8962, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31290487

RESUMO

Hydrocarbon stapled peptides are promising therapeutics for inhibition of intracellular protein-protein interactions. Here we develop a new high-throughput strategy for hydrocarbon stapled peptide discovery based on mRNA display of peptides containing α-methyl cysteine and cyclized with m-dibromoxylene. We focus on development of a peptide binder to the HPV16 E2 protein.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Evolução Molecular Direcionada/métodos , Proteínas Nucleares/metabolismo , Proteínas Oncogênicas Virais/metabolismo , Peptídeos/metabolismo , Engenharia de Proteínas/métodos , Fatores de Transcrição/metabolismo , Alquilação , Sequência de Aminoácidos , Ciclização , Cisteína/química , Hidrocarbonetos Bromados/química , Biblioteca de Peptídeos , Peptídeos/química , Ligação Proteica/efeitos dos fármacos , RNA Mensageiro/química
17.
J Agric Food Chem ; 67(30): 8370-8381, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31271280

RESUMO

Naturally occurring dietary peptides derived from gastrointestinal digestates of common bean milk and yogurt were studied for their bioaccessibility, bioavailability, and anti-inflammatory activity in both Caco-2 mono- and Caco-2/EA.hy926 co-culture cell models. Anti-inflammatory activities of these peptide extracts were found to be strongly associated with cellular uptake by the intestinal epithelial cells. Mechanisms underlying the cellular uptake were studied by examining the role of peptide transporter 1 and calcium sensing reporter. Three peptides, including γ-glutamyl-S-methylcysteine, γ-glutamyl-leucine, and leucine-leucine-valine, were found to be transported across the Caco-2 cell monolayer and detected by liquid chromatography-tandem mass spectrometry. A strong anti-inflammatory effect was observed in the basolateral EA.hy926 cells (co-culture model), as shown in their inhibition of tumor necrosis factor α-induced pro-inflammatory mediators of the nuclear factor κB and mitogen-activated protein kinase signal cascades. The results suggest that these peptides can be absorbed and possibly have systemic inhibition on inflammatory responses in vascular endothelial cells, indicating potential preventive effects on vascular diseases.


Assuntos
Anti-Inflamatórios/metabolismo , Células Endoteliais/metabolismo , Peptídeos/metabolismo , Phaseolus/química , Extratos Vegetais/metabolismo , Iogurte/análise , Transporte Biológico , Células CACO-2 , Técnicas de Cocultura , Células Epiteliais/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Intestinos/citologia , NF-kappa B/genética , NF-kappa B/metabolismo , Transportador 1 de Peptídeos/genética , Transportador 1 de Peptídeos/metabolismo , Peptídeos/química , Phaseolus/metabolismo , Extratos Vegetais/química
18.
Chem Commun (Camb) ; 55(62): 9072-9075, 2019 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-31268098

RESUMO

We constructed GFP-encapsulated microtubules (MTs) using a Tau-derived peptide which binds to their interior. The encapsulation of the GFP dramatically increased the rigidity of MTs, resulting in their enhanced velocity on a kinesin-coated substrate. Moreover, the GFP-encapsulated MTs were significantly more stable than normal MTs.


Assuntos
Proteínas de Fluorescência Verde/química , Microtúbulos/química , Peptídeos/química , Proteínas tau/química , Modelos Moleculares , Tamanho da Partícula , Propriedades de Superfície
19.
Chem Commun (Camb) ; 55(62): 9108-9111, 2019 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-31298230

RESUMO

Inhibition of myostatin is an attractive treatment for muscular dystrophy and other amyotrophic diseases. A myostatin-binding peptide was functionalized by equipped with an on/off switchable photo-oxygenation catalyst. This peptide induces a selective oxygenation of myostatin under near-infrared light, resulting in inactivation of myostatin. This peptide shows several orders of magnitude greater inhibitory effect than the original peptide.


Assuntos
Miostatina/efeitos dos fármacos , Miostatina/efeitos da radiação , Oxigênio/química , Oxigênio/efeitos da radiação , Peptídeos/farmacologia , Processos Fotoquímicos/efeitos da radiação , Catálise/efeitos dos fármacos , Catálise/efeitos da radiação , Humanos , Raios Infravermelhos , Modelos Moleculares , Estrutura Molecular , Miostatina/metabolismo , Peptídeos/química
20.
Phys Chem Chem Phys ; 21(29): 16198-16206, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31298234

RESUMO

The secondary structure of proteins is of prime importance to their proper functioning and protein misfolding may cause serious disorders in the human body. Here, the electric field influence on the conformational stability of model alpha helical peptides is studied by employing density functional theory calculations combined with continuum dielectric method computations. Our results show that the basic parameters of the electric field - its strength and directionality - are determinative for the alpha helix stability. An electric field strength of 0.005 a.u. (2.5 V nm-1) applied along the X coordinate axis (the long axis of the helix) in the direction of the µx component of the molecular dipole moment does affect the peptide conformation, destroys the helix, and leads to the formation of a cyclic-peptide-like structure. Interestingly, the process of denaturation can be reversible when the electric field is switched-off. The reversibility of the process of the electric field induced disruption of the peptide secondary structure suggests a possible mechanism for the healing of misfolded proteins.


Assuntos
Fenômenos Eletromagnéticos , Modelos Químicos , Peptídeos/química , Peptídeos/efeitos da radiação , Conformação Proteica em alfa-Hélice , Dobramento de Proteína/efeitos da radiação
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