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1.
Macromol Biosci ; : e2000199, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32852141

RESUMO

A new general method to covalently link a peptide to cotton via thiazolidine ring formation is developed. Three different analogues of an ultrashort antibacterial peptide are synthesized to create an antibacterial fabric. The chemical ligation approach to the heterogeneous phase made up of insoluble cellulose fibers and a peptide solution in water is adapted. The selective click reaction occurs between an N-terminal cysteine on the peptide and an aldehyde on the cotton matrix. The aldehyde is generated on the primary alcohol of glucose by means of the enzyme laccase and the cocatalyst 2,2,6,6-tetramethylpiperidine-1-oxyl. This keeps the pyranose rings intact and may bring a benefit to the mechanical properties of the fabric. The presence of the peptide on cotton is demonstrated through instant colorimetric tests, UV spectroscopy, IR spectroscopy, and X-ray photoelectron spectroscopy analysis. The antibacterial activity of the peptides is maintained even after their covalent attachment to cotton fibers.

2.
J Magn Reson ; 309: 106621, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31669794

RESUMO

In frozen biological media and molecular glasses only restricted motions exist; because of the weakness and disorder of intermolecular bonds these motions may have stochastic nature. Electron spin echo (ESE) spectroscopy of spin-labeled molecules allows detecting their restricted stochastic rotations (stochastic molecular librations). As in molecular disordered media motions may be highly cooperative, it would be desirable to investigate their spectroscopic manifestation also in the systems where cooperative effects would be certainly ruled out. In this work, ESE of spin-labeled molecules adsorbed on inorganic SiO2 surface was investigated in a wide temperature range. The rate of motion-induced spin relaxation was found to become measurable above 130 K, increasing with temperature and attaining then a saturating behavior with a well-defined maximum near 250 K. For two types of molecules differing remarkably in their size and polarity (a small highly-polar nitroxide radical and a large spin-labeled peptide), quite similar results were obtained. This saturating behavior was quantitatively reproduced in simulations within a simple model of jump between two close orientations. Comparison with experiment allowed estimate that at 250 K the correlation time of the motion τc is of the order of several tens of nanoseconds and the angle α between two orientations is around 0.02 rad. As the found saturating behavior is a property of individual motions, for any other molecular system an excess of the spin relaxation rate above the maximum found here for adsorbed molecules may be ascribed to cooperative motions. Comparison with literature data on molecular systems of different origin has shown that effects of cooperativity indeed are present and, moreover, may be very essential.

3.
Phys Chem Chem Phys ; 21(41): 23217, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31602454

RESUMO

Correction for 'An EPR study of ampullosporin A, a medium-length peptaibiotic, in bicelles and vesicles' by Marco Bortolus et al., Phys. Chem. Chem. Phys., 2016, 18, 749-760.

4.
Chembiochem ; 20(16): 2125-2132, 2019 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-31095838

RESUMO

Trichogin is a natural peptide endowed with antimicrobial and antitumor activity. A member of the peptaibol family, trichogin possesses a C-terminal amino alcohol. In the past, this moiety was substituted for a methyl ester for synthetic purposes and it was observed that this apparently slight modification caused significant changes in the peptide bioactivity. With the aim of understanding the reasons behind such observations, a detailed spectroscopic study on a number of trichogin analogues has been performed. Herein, data obtained from synchrotron radiation circular dichroism, NMR spectroscopy, and fluorescence spectroscopy in organic solvents at cryogenic temperatures are compared with those independently acquired by means of EPR spectroscopy at 80 K. It is unambiguously revealed that the presence of a reversible, temperature-driven, screw-sense interconversion from a right- to left-handed helix is determined by the C-terminal capping moiety. Data demonstrate, for the first time, the key role of a C-terminal methyl ester in promoting peptide screw-sense inversion.

5.
Front Chem ; 7: 170, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984741

RESUMO

Tumor angiogenesis, essential for cancer development, is regulated mainly by vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs), which are overexpressed in cancer cells. Therefore, the VEGF/VEGFR interaction represents a promising pharmaceutical target to fight cancer progression. The VEGF surface interacting with VEGFRs comprises a short α-helix. In this work, helical oligopeptides mimicking the VEGF-C helix were rationally designed based on structural analyses and computational studies. The helical conformation was stabilized by optimizing intramolecular interactions and by introducing helix-inducing Cα,α-disubstituted amino acids. The conformational features of the synthetic peptides were characterized by circular dichroism and nuclear magnetic resonance, and their receptor binding properties and antiangiogenic activity were determined. The best hits exhibited antiangiogenic activity in vitro at nanomolar concentrations and were resistant to proteolytic degradation.

6.
Front Chem ; 7: 192, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31001518

RESUMO

α,ß2,3-Disteroisomeric foldamers of general formula Boc(S-Ala-ß-2R,3R-Fpg)nOMe or Boc(S-Ala-ß-2S,3S-Fpg)nOMe were prepared from both enantiomers of syn H-2-(2-F-Phe)-h-PheGly-OH (named ß-Fpg) and S-alanine. Our peptides show two appealing features for biomedical applications: the presence of fluorine, attractive for non-covalent interactions, and aryl groups, crucial for π-stacking. A conformational study was performed, using IR, NMR and computational studies of diastereoisomeric tetra- and hexapeptides containing the ß2,3-amino acid in the R,R- and S,S-stereochemistry, respectively. We found that the stability of peptide conformation is dependent on the stereochemistry of the ß-amino acid. Combining S-Ala with ß-2R,3R-Fpg, a stable extended ß-strand conformation was obtained. Furthermore, ß-2R,3R-Fpg containing hexapeptide self-assembles to form antiparallel ß-sheet structure stabilized by intermolecular H-bonds and π,π-interactions. These features make peptides containing the ß2,3-fluoro amino acid very appealing for the development of bioactive proteolytically stable foldameric ß-sheets as modulators of protein-protein interaction (PPI).

7.
J Pept Sci ; 25(5): e3165, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30916858

RESUMO

α-Amino acid residues with a ϕ,ψ constrained conformation are known to significantly bias the peptide backbone 3D structure. An intriguing member of this class of compounds is (αMe)Aze, characterized by an Nα -alkylated four-membered ring and Cα -methylation. We have already reported that (S)-(αMe)Aze, when followed by (S)-Ala in the homochiral dipeptide sequential motif -(S)-(αMe)Aze-(S)-Ala-, tends to generate the unprecedented γ-bend ribbon conformation, as formation of a regular, fully intramolecularly H-bonded γ-helix is precluded, due to the occurrence of a tertiary amide bond every two residues. In this work, we have expanded this study to the preparation and 3D structural analysis of the heterochiral (S)-Ala/(R)-(αMe)Aze sequential peptides from dimer to hexamer. Our conformational results show that members of this series may fold in type-II ß-turns or in γ-turns depending on the experimental conditions.


Assuntos
Alanina/química , Ácido Azetidinocarboxílico/química , Oligopeptídeos/química , Oligopeptídeos/síntese química , Ressonância Magnética Nuclear Biomolecular , Conformação Proteica , Difração de Raios X
8.
Langmuir ; 35(14): 4813-4824, 2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30864802

RESUMO

The cyclic change of structure, thickness, and density, with pH switching from acidic (pH = 3) to basic (pH = 11) condition, has been revealed for chemisorbed monolayers of the peptide Lipo-Aib-Lys-Leu-Aib-Lys-Lys-Leu-Aib-Lys-Ile-Lol, a trichogin GA IV-analogue carrying Lys residues instead of Gly ones at positions 2, 5, 6, and 9, while a homologous peptide not containing Lys residues does not show any response to pH changes. Experimental and theoretical results, obtained by means of quartz crystal microbalance with dissipation monitoring, surface plasmon resonance, nanoplasmonic sensing technique, Fourier transform infrared-reflection attenuated spectroscopy and dynamic force spectroscopy, and molecular dynamics simulations provide detailed information on the overall monolayer structure changes with pH, including the analysis of the intra- and interchain peptide dynamics, the structure of the peptide layer/water/solid interface, as well as the position and role of solvation and nonsolvation water. The observed stimuli-responsive behavior of L1 peptide monolayers is accounted in terms of the occurrence of a pH-induced wetting/dewetting process, due to the pH-induced switching of the hydrophilic character of charged lysine groups to hydrophobic one of the same uncharged groups, along the peptide chain. This behavior in turn promotes the collective change of the aggregation state of the peptide chains. The present results may pave the way to critically reexamine the mechanism of stimuli-responsive systems.

9.
Biochim Biophys Acta Biomembr ; 1861(2): 524-531, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30550880

RESUMO

The antimicrobial action of peptides in bacterial membranes is commonly related to their mode of self-assembling which results in pore formation. To optimize peptide antibiotic use for therapeutic purposes, a study on the concentration dependence of self-assembling process is thus desirable. In this work, we investigate this dependence for peptaibol trichogin GA IV (Tric) in the 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) model membrane in the range of peptide concentrations between 0.5 and 3.3 mol%. Pulsed double electron-electron resonance (PELDOR) applied on spin-labeled peptide analogs highlights the onset of peptide dimerization above a critical peptide concentration value, namely ~ 2 mol%. Electron spin echo (ESE) envelope modulation (ESEEM) for D2O-hydrated bilayers shows that dimerization is accompanied by peptide re-orientation towards a trans-membrane disposition. For spin-labeled stearic acids (5-DSA) in POPC bilayers, the study of ESE decays and ESEEM in the presence of a deuterated peptide analog indicates that above the critical peptide concentration the 5-DSA molecules are attracted by peptide molecules, forming nanoclusters. As the 5-DSA molecules represent a model for the behavior of fatty acids participating in bacterial membrane homeostasis, such capturing action by Tric may represent an additional mechanism of its antibiotic activity.


Assuntos
Antibacterianos/farmacologia , Ácidos Graxos/química , Bicamadas Lipídicas/química , Lipopeptídeos/farmacologia , Peptídeos/farmacologia , Sequência de Aminoácidos , Dimerização , Espectroscopia de Ressonância de Spin Eletrônica , Fosfatidilcolinas/química , Ácidos Esteáricos/química , Água/química
10.
Chempluschem ; 84(11): 1688-1696, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31943881

RESUMO

The influence of conformational dynamics on the self-assembly process of a conformationally constrained analogue of the natural antimicrobial peptide Trichogin GA IV was analysed by spectroscopic methods, microscopy imaging at nanometre resolution, and molecular dynamics simulations. The formation of peptide films at the air/water interface and their deposition on a graphite or a mica substrate were investigated. A combination of experimental evidence with molecular dynamics simulation was used to demonstrate that only the fully developed helical structure of the analogue promotes formation of ordered aggregates that nucleate the growth of micrometric rods, which give rise to homogenous coating over wide regions of the hydrophilic mica. This work proves the influence of helix flexibility on peptide self-organization and orientation on surfaces, key steps in the design of bioinspired organic/inorganic hybrid materials.


Assuntos
Silicatos de Alumínio/química , Grafite/química , Lipopeptídeos/química , Nanoestruturas/química , Sequência de Aminoácidos , Microscopia de Força Atômica , Simulação de Dinâmica Molecular , Propriedades de Superfície , Água/química , Difração de Raios X
11.
Org Biomol Chem ; 16(42): 7947-7958, 2018 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-30318540

RESUMO

Unlike the extensively investigated relationship between the peptide ß-bend ribbon and its prototypical 310-helix conformation, the corresponding relationship between the narrower γ-bend ribbon and its regular γ-helix counterpart still remains to be studied, as the latter 3D-structures have not yet been experimentally authenticated. In this paper, we describe the results of the first characterization, both in the crystal state and in solution, of the γ-bend ribbon conformation using X-ray diffraction and FT-IR absorption, electronic CD and 2D-NMR spectroscopies applied to an appropriate set of synthetic, homo-chiral, sequential dipeptide oligomers based on (S)-Ala and the known γ-bend inducer, Cα-tetrasubstituted, N-alkylated α-amino acid residue (S)-Cα-methyl-azetidine-carboxylic acid.

12.
J Phys Chem B ; 122(24): 6305-6313, 2018 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-29792795

RESUMO

Peptide self-assembly is ubiquitous in nature. It governs the organization of proteins, controlling their folding kinetics and preserving their structural stability and bioactivity. In this connection, model oligopeptides may give important insights into the molecular mechanisms and elementary forces driving the formation of supramolecular structures. In this contribution, we show that a single residue substitution, that is, Aib (α-aminoisobutyric acid) in place of Ala at position 4 of an -(l-Ala)5-homo-oligomer, strongly alters the aggregation process. In particular, this process is initiated by the formation of small peptide clusters that promote aggregation on the nanometer scale and, through a hierarchical self-assembly, lead to mesoscopic structures of micrometric dimensions. Furthermore, we show that the use of the well-established Langmuir-Blodgett technique represents an effective strategy for coating extended areas of inorganic substrates by densely packed peptide layers, thus paving the way for application of peptide films as templates for biomineralization, biocompatible coating of surfaces, and scaffolds for tissue engineering.


Assuntos
Nanoestruturas/química , Oligopeptídeos/química , Ar , Ácidos Aminoisobutíricos/química , Microscopia de Força Atômica , Simulação de Dinâmica Molecular , Oligopeptídeos/metabolismo , Estrutura Secundária de Proteína , Espectrometria de Fluorescência , Água/química
13.
ChemMedChem ; 13(11): 1131-1145, 2018 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-29570944

RESUMO

Five new AuIII -peptidodithiocarbamato complexes of the type [AuIII Br2 (dtc-AA1 -AA2 -OR] (in which AA1 =N-methylglycine (Sar), l/d-Pro; AA2 =l/d-Ala, α-aminoisobutyric acid (Aib); R=OtBu, triethylene glycol methyl ether), differing with regard to the amino acid sequence and/or the chiral amino acid configuration, were designed to enhance tumor selectivity and bioavailability. The gold(III)-based moiety was functionalized to exploit the targeting properties of the peptidomimetic ligand toward two peptide transporters (namely PEPT1 and PEPT2), which are upregulated in several tumor cells. The compounds were synthesized and fully characterized, mainly by means of elemental analysis, one- and two-dimensional NMR spectroscopy, FT-IR, and UV/Vis spectrophotometry. The crystal structures of three compounds were also solved by X-ray diffraction. In vitro cytotoxicity studies using a panel of human tumor cell lines (A549 [non-small-cell lung carcinoma], MCF-7 [breast cancer], A2780 [ovarian carcinoma], H1975 [non-small-cell lung carcinoma], H460 [large-cell lung carcinoma], and A431 [human epidermoid carcinoma]) showed the dtc-Pro-Aib-OtBu derivative to be very effective, with GI50 values much lower than those of cisplatin. This complex was thus selected for evaluating stability under physiological conditions and possible interactions with serum albumin, as well in PARP-1 enzyme inhibition assays and preliminary ex vivo toxicity experiments on healthy rat tissues.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Ouro/química , Peptidomiméticos/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Antineoplásicos/toxicidade , Bovinos , Linhagem Celular Tumoral , Colo/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/metabolismo , Complexos de Coordenação/toxicidade , Ensaios de Seleção de Medicamentos Antitumorais , Ensaios Enzimáticos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/toxicidade , Humanos , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Peptidomiméticos/síntese química , Peptidomiméticos/metabolismo , Peptidomiméticos/toxicidade , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Ligação Proteica , Ratos , Soroalbumina Bovina/metabolismo , Estereoisomerismo
14.
Phys Chem Chem Phys ; 20(5): 3592-3601, 2018 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-29340383

RESUMO

The antimicrobial action of the peptide antibiotic alamethicin (Alm) is commonly related to peptide self-assembling resulting in the formation of voltage-dependent channels in bacterial membranes, which induces ion permeation. To obtain a deeper insight into the mechanism of channel formation, it is useful to know the dependence of self-assembling on peptide concentration. With this aim, we studied Alm F50/5 spin-labeled analogs in a model 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membrane, for peptide-to-lipid (P/L) ratios varying between 1/1500 and 1/100. Pulsed electron-electron double resonance (PELDOR) spectroscopy reveals that even at the lowest concentration investigated, the Alm molecules assemble into dimers. Moreover, under these conditions, electron spin echo envelope modulation (ESEEM) spectroscopy of D2O-hydrated membranes shows an abrupt change from the in-plane to the trans-membrane orientation of the peptide. Therefore, we hypothesize that dimer formation and peptide reorientation are concurrent processes and represent the initial step of peptide self-assembling. By increasing peptide concentration, higher oligomers are formed. A simple kinetic model of equilibrium among monomers, dimers, and pentamers allows for satisfactorily describing the experimental PELDOR data. The inter-label distances in the oligomers obtained from PELDOR experiments become better resolved with increasing P/L ratio, thus suggesting that the supramolecular organization of the higher-order oligomers becomes more defined.


Assuntos
Alameticina/química , Bicamadas Lipídicas/química , Alameticina/metabolismo , Sequência de Aminoácidos , Dimerização , Espectroscopia de Ressonância de Spin Eletrônica , Cinética , Bicamadas Lipídicas/metabolismo , Fosfatidilcolinas/química , Marcadores de Spin , Água/química
15.
Biopolymers ; 2017 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-29127716

RESUMO

In this work, an extensive set of spectroscopic and biophysical techniques (including FT-IR absorption, CD, 2D-NMR, fluorescence, and CW/PELDOR EPR) was used to study the conformational preferences, membrane interaction, and bioactivity properties of the naturally occurring synthetic 14-mer peptaibiotic chalciporin A, characterized by a relatively low (≈20%), uncommon proportion of the strongly helicogenic Aib residue. In addition to the unlabeled peptide, we gained in-depth information from the study of two labeled analogs, characterized by one or two residues of the helicogenic, nitroxyl radical-containing TOAC. All three compounds were prepared using the SPPS methodology, which was carefully modified in the course of the syntheses of TOAC-labeled analogs in view of the poorly reactive α-amino function of this very bulky residue and the specific requirements of its free-radical side chain. Despite its potentially high flexibility, our results point to a predominant, partly amphiphilic, α-helical conformation for this peptaibiotic. Therefore, not surprisingly, we found an effective membrane affinity and a remarkable penetration propensity. However, chalciporin A exhibits a selectivity in its antibacterial activity not in agreement with that typical of the other members of this peptide class.

16.
J Org Chem ; 82(19): 10033-10042, 2017 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-28858505

RESUMO

The intrinsically blue-colored Ullman imidazolinyl nitronyl nitroxide (NN) mono-radicals have found various applications, in particular as spin probes and organic magnetic materials. Here, we present the solution-phase synthesis, extensive characterization, and conformational analysis of the first peptidomimetics with two pendant, chiral nitronyl nitroxide free radical units. Two (R)-Aic(NN) residues, where Aic(NN) is 2-amino-5-nitronylnitroxide-indan-2-carboxylic acid, have been inserted at positions i and i+3 of the pentapeptide Boc-(R)-Aic(NN)-(Ala)2-(R)-Aic(NN)-Ala-OMe and the hexapeptide Boc-[Ala-(R)-Aic(NN)-Ala]2-OMe as well. The two compounds were obtained in good yields and high purities. Thanks to a combination of several spectroscopic techniques (IR absorption, NMR, VCD, and EPR) we gained clear evidence that both compounds adopt a right-handed 310-helical conformation with both nitronyl nitroxide pendants positioned on the same side of the helix. This peptidomimetic/free radical system is a potentially excellent template for the preparation of a set of appropriate analogs with exciting applications in the area of host-guest organic chemistry, or to spectroscopically evaluate in-depth the intramolecular exchange interactions in this type of probe.

17.
Nanomedicine ; 13(8): 2575-2585, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28756094

RESUMO

A creation of nanotraps that could selectively recognize the chemotactic mediators of leukocyte adhesion and eliminate them from the bloodstream and tissue intercellular matrix is a promising approach for the treatment of various inflammatory and autoimmune diseases. We designed nanotraps as artificial decoy receptors based on poly(lactic acid) (PLA) nanoparticles covered by heparin and bearing on the surface two fragments of CCR5 receptor (N-terminal domain, Nt, and second extracellular loop, ECL2), responsible for chemokine binding. In order to attach Nt and ECL2 to the heparin shell, the corresponding peptides were modified with N- and/or C-terminal oligolysines. The presence of the nanotraps in the cell medium completely eliminated the activating effect of a CCR5 ligand, chemokine Rantes, while strongly decreasing the adhesion of monocytes to the human endothelial cells. We found that the modified ECL2 alone was also able to prevent monocyte adhesion, thus acting as a decoy receptor itself.


Assuntos
Materiais Biomiméticos/química , Quimiocinas/isolamento & purificação , Proteínas Imobilizadas/química , Receptores CCR5/química , Biomimética , Adesão Celular , Células Hep G2 , Heparina/química , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamação/terapia , Modelos Moleculares , Nanomedicina , Poliésteres/química , Propriedades de Superfície
18.
J Phys Chem B ; 121(17): 4379-4387, 2017 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-28422504

RESUMO

We address the interpretation, via an integrated computational approach, of the experimental continuous-wave electron paramagnetic resonance (cw-EPR) spectra of a complete set of conformationally highly restricted, stable 310-helical peptides from hexa- to nonamers, each bis-labeled with nitroxide radical-containing TOAC (4-amino-1-oxyl-2,2,6,6-tetramethylpiperidine-4-carboxylic acid) residues. The usefulness of TOAC for this type of analysis has been shown already to be due to its cyclic piperidine side chain, which is rigidly connected to the peptide backbone α-carbon. The TOAC α-amino acids are separated by two, three, four, and five intervening residues. This set of compounds has allowed us to modulate both the radical···radical distance and the relative orientation parameters. To further validate our conclusion, a comparative analysis has been carried out on three singly TOAC-labeled peptides of similar main-chain length.


Assuntos
Óxidos N-Cíclicos/química , Óxidos de Nitrogênio/química , Peptídeos/química , Teoria Quântica , Espectroscopia de Ressonância de Spin Eletrônica , Marcadores de Spin
19.
J Pept Sci ; 23(2): 104-116, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28054413

RESUMO

The role of the conformationally constrained α-aminoisobutyric acid (Aib) residue in the aggregation and self-assembly properties of oligopeptides is discussed, critically reviewing our recent work in the field. In this connection, three significant case studies are presented: (i) aggregation propensity of Aib homo-oligopeptides of different length; (ii) perturbation of the conformational and aggregation properties of Ala-based pentapeptides by a single Aib versus Ala substitution; and (iii) build up of self-assembled monolayers formed by Aib homo-hexapeptide building blocks. The peptides investigated were all functionalized by a fluorescent probe, that is, a naphthyl group in the first case-study and a pyrenyl group in the other two, with the aim at applying optical spectroscopy techniques and evaluating the relevance of aromatic interactions in the aggregation process. Microscopy techniques at nanometric resolution and results of molecular dynamics simulations are also presented to analyze how the conformational properties of the peptide building blocks would affect the morphology of the peptide aggregates from the nanoscale to the mesoscale. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.


Assuntos
Ácidos Aminoisobutíricos/química , Oligopeptídeos/química , Agregados Proteicos , Sequência de Aminoácidos , Corantes Fluorescentes/química , Ligação de Hidrogênio , Microscopia de Força Atômica , Simulação de Dinâmica Molecular , Sondas Moleculares/química , Estrutura Secundária de Proteína , Soluções , Espectrometria de Fluorescência
20.
Biopolymers ; 108(1)2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27404945

RESUMO

In this study, we performed a detailed literature survey of the ɛ-turn in peptides and proteins. This three-dimensional structural feature is characterized by an eleven-membered pseudo-cycle closed by an intramolecular backbone…backbone H-bond. Interestingly, in this motif the direction of the N-H…O = C H-bond runs opposite to that of the much more popular and extensively investigated α-, ß-, and γ-turns. We did not authenticate unequivocally the ɛ-turn main-chain reversal topology in any linear short peptide. However, it is frequently observed in small cyclic peptides formed by four, five, and six amino acid residues with stringent geometric requirements. Rather surprisingly, ɛ-turns do occur in proteins, although to a relatively moderate extent, as an isolated feature or in the turn segment of hairpin motifs based on two antiparallel, pleated ß-strands. Moreover, the ɛ-turn may also host not only the seven-membered, intramolecularly H-bonded, pseudo-cycle termed γ-turn, either of the classic or inverse type, but also one (or even two) cis peptide bond(s) or a ß-bulge conformation. Based on their ϕ, ψ backbone torsion angles, we were able to classify the protein ɛ-turns in six different families. Conformational energy computations using the DFT methodology were also performed on the ɛ-turns adopted by the amino acid triplet -Gly-Gly-Gly- (Gly is the most commonly found residue at each of the three positions in our analysis of proteins). Again, in this computational study, six families of turns were identified, but only some of them resemble rather closely those extracted from our investigation on proteins.


Assuntos
Peptídeos/química , Sequência de Aminoácidos , Cristalografia por Raios X , Ligação de Hidrogênio , Isomerismo , Espectroscopia de Ressonância Magnética , Oligopeptídeos/química , Peptídeos Cíclicos/química , Estrutura Secundária de Proteína , Proteínas/química
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