Rebeca Garcia-Fandino

Rebeca Garcia-Fandino
University of Porto | UP · FACULDADE DE CIÊNCIAS DA UNIVERSIDADE DO PORTO

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73
Publications
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Publications

Publications (73)
Article
Hipothesis: Membranes based on cyclodextrin complexes can be used as functional nanocarrier envelopers by chemical modifications of the cyclodextrin hydroxyl groups or by encapsulating different ligands in their cavities. Experiments: Molecular dynamics simulations of monolayers and bilayers based on supramolecular complexes consisting of two α or...
Article
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In analogy with the hierarchical levels typically used to describe the structure of nucleic acids or proteins and keeping in mind that lipid bilayers are not just mere envelopers for biological material but directly responsible for many important functions of life, it is discussed here how membrane models can also be interpreted in terms of differe...
Article
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Self-assembled cyclic peptide nanotubes with alternating D- and L-amino acid residues in the sequence of each subunit have attracted a great deal of attention due to their potential for new nanotechnology and biomedical applications, mainly in the field of antimicrobial peptides. Molecular dynamics simulations can be used to characterize these syst...
Article
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Host defence peptides (HDPs) are short cationic peptides that play a key role in the innate immune response of all living organisms. Their action mechanism does not depend on the presence of protein receptors, but on their ability to target and disrupt the membranes of a wide range of pathogenic and pathologic cells which are recognized by their sp...
Article
Fluorescence spectroscopy is used to characterize the partition of three second-generation D,L-α-cyclic peptides to two lipid model membranes. The peptides have proven antimicrobial activity, particularly against Gram positive bacteria, and the model membranes are formed of either with 1,2-dimyristoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DMPG) o...
Article
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The formation of small hybrid aggregates between excipient and drug molecules is one of the mechanisms that contributes to the solubilization of active principles in pharmaceutical formulations. The characterization of the formation, governing interactions and structure of such entities is not trivial since they are highly flexible and dynamic, qui...
Article
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Interest in lipid interactions with proteins and other biomolecules is emerging not only in fundamental biochemistry but also in the field of nanobiotechnology where lipids are commonly used, for example, in carriers of mRNA vaccines. The outward-facing components of cellular membranes and lipid nanoparticles, the lipid headgroups, regulate membran...
Article
Modified cyclodextrins (CDs) consist of a distribution of different structures with different number and location of the substituted groups. Among the most important applications of these molecules is their use as an enabling excipient in pharmaceutical formulations to provide the necessary solubility, stability and bioavailability for a drug to be...
Article
Antimicrobial peptides are viewed as a promising alternative to conventional antibiotics, as their activity through membrane targeting makes them less prone to resistance development. Among them, antimicrobial D,L-α-cyclic peptides (CPs) have been proposed as an alternative, specially due to their cyclic nature and to the presence of D- amino acids...
Article
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Self-assembling cyclic peptide nanotubes have been shown to function as synthetic, integral transmembrane channels. The combination of natural and nonnatural aminoacids in the sequence of cyclic peptides enables the control not only of their outer surface but also of the inner cavity behavior and properties, affecting, for instance, their permeabil...
Article
We have developed a novel class of specifically engineered, dimerized cyclodextrin nanostructures for the encapsulation of toxic biomolecules such as 7-ketocholesterol (7KC). 7KC accumulates over time and causes dysfunction in many cell types, linking it to several age-related diseases including atherosclerosis and age-related macular degeneration...
Article
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Self-assembling cyclic peptide nanotubes can form nanopores when they are inserted in lipid bilayers, acting as ion and/or water permeable channels. In order to improve the versatility of these systems, it is possible to specifically design cyclic peptides with a combination of natural and non-natural amino acids, enabling the control of the nature...
Article
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In contrast to other pathogenic agents that directly destroy host cells and tissues, the lethal power of SARS-CoV-2 resides in the over-reactive immune response triggered by this virus. Based on numerous evidences indicating that the lipid composition of host membranes is dramatically affected by COVID-19, and in the fact that our endogenous antimi...
Article
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In this work we report a rational design strategy for the identification of new peptide prototypes for the non-disruptive supramolecular permeation of membranes and the transport of different macromolecular giant cargos. The approach targets a maximal enhancement of helicity in the presence of membranes with sequences bearing the minimal number of...
Article
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The era of the explosion of immersive technologies has bumped head-on with the coronavirus disease 2019 (COVID-19) global pandemic caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The proper understanding of the three-dimensional structures that compose the virus, as well as of those involved in the infection process and...
Article
A handful of singular structures and laws can be observed in nature. They are not always evident but, once discovered, it seems obvious how to take advantage of them. In chemistry, the discovery of reproducible patterns stimulates the imagination to develop new functional materials and technological or medical applications. Two clear examples are h...
Article
Rational design and development of new nanosystem usually relies on empirical approaches as well as a fair degree of serendipity. Understanding how nanosystems behave at molecular level is of great importance for potential biomedical applications. In this work we describe a nanosystem composed by two natural compounds, Vitamin E and Sphingomyelin,...
Article
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We describe the discovery of unprecedented annulation processes of 1,7-allenedienes, promoted by Pt or Au catalysts. These transformations allowed to unveil mechanistic pathways that had not been previously observed in reactions involving carbophilic catalysis. In particular, we have found that allenedienes bearing a silyl ether at the carbon tethe...
Article
Full-text available
The basket-like geometry of cyclodextrins (CDs), with a cavity able to host hydrophobic groups, makes these molecules well suited for a large number of fundamental and industrial applications. Most of the established CD-based applications rely on trial and error studies, often ignoring key information at the atomic level that could be employed to d...
Article
Cyclic peptides with disc‐shaped structures have emerged as potent building blocks for the preparation of new biomaterials in fields ranging from biological to material science. In this work, we analyze in deep the self‐assembling properties of a new type of cyclic peptides based on the alternation of α‐residues and cyclic δ‐amino acids (α,δ‐CPs)....
Article
A cyclic hexapeptide with three pyridyl moieties connected to its backbone forms a hydrogen-bonded dimer, which tightly encapsulates a single xenon atom, like a pearl in its shell. The dimer imprints its shape and symmetry to the captured xenon atom, as demonstrated by 129 Xe NMR spectroscopy, single-crystal X-ray diffraction, and computational stu...
Article
Eng eingeschlossen: Ein cyclisches Hexapeptid mit drei Pyridylgruppen an der Hauptkette bildet ein wasserstoffbrückengebundenes Dimer, das ein einzelnes Xenon‐Atom eng einkapselt. Die Dimere ordnen sich hierarchisch zu röhrenartigen Strukturen in einer porösen supramolekularen Architektur an, deren Hohlräume durch kleine Moleküle und Gase ausgefüll...
Article
"Intelligent" materials based on synthetic small molecules that become functional only under specific conditions provide new opportunities for developing regulated systems aimed to a large number of applications. For instance, biologically active supramolecular entities that are sensitive to environmental conditions, such as the presence of bacteri...
Article
o‐Alkenyl‐N‐triflylanilides undergo Rh(III)‐catalyzed oxidative annulations with alkynes to produce different types of naphthylamides, in a process which involves the cleavage of two C‐H bonds. Remarkably, in addition to formal dehydrogenative (4C+2C) cycloadducts, the reaction also produces variable amounts of isomeric naphthylamides whose formati...
Article
o‐Alkenyl‐N‐triflylanilides undergo Rh(III)‐catalyzed oxidative annulations with alkynes to produce different types of naphthylamides, in a process which involves the cleavage of two C‐H bonds. Remarkably, in addition to formal dehydrogenative (4C+2C) cycloadducts, the reaction also produces variable amounts of isomeric naphthylamides whose formati...
Chapter
Cyclic peptides (CPs) belong to an interesting class of peptides that have been widely studied over the past decades. This class of peptides has been applied in different fields, such as the pharmaceutical industry (due to their antibacterial or antitumor activity), agricultural applications (as fungicides), diagnostics, and vaccines.One of the mai...
Article
A new method for switching between structures consisting of equivalent discrete and flexible objects with different particle representation and object configuration, including different resolution levels (number of particles per object), is reported. The method is fully general since it does not require any extra code nor additional database elemen...
Article
Full-text available
We have generated a site-directed mutant of the manganese superoxide dismutase SOD-3 of C.elegans (MnSOD-3) which modifies the metal specificity of the enzyme. While wild-type MnSOD-3 functions with manganese in the active site (3600 U.mg protein-1) it has little or no activity when iron is incorporated. However, when histidine replaces glutamine 1...
Chapter
Membrane channels are transmembrane-spanning structures that have an internal cavity that allow the migration of different ions and molecules. Inspired by the natural systems, chemists have created a variety of synthetic mimicries. Frequently, self-assembling methods were used to prepare the complex structure of these molecular channels. Although i...
Article
Gene transfection continues to be a major challenge in chemistry, biology and materials sciences. New methodologies and recent breakthroughs have renewed the interest in the discovery and development of new tools for efficient gene transfection. Hydrazone formation between a cationic head and hydrophobic tails has emerged as one of the most promisi...
Article
A new cyclic peptide dimer that encapsulates cisplatin complexes in its internal cavity is described. The resulting complex showed cytotoxic activity at A2780 ovarian cancer cell lines independent of acquired platinum resistance.
Article
2-Alkenyltriflylanilides react with allenes upon treatment with catalytic amounts of Pd(OAc)2 and Cu(II) to give highly valuable 2,3-dihydro-1H-benzo[b]azepines, in good yields, and with very high regio- and diastereoselectivities. Density functional theory (DFT) calculations suggest that the C–H activation of the alkenylanilide involves a classica...
Research
Full-text available
Cyclodextrins (CDs) are amongst the most versatile/multi-functional molecules used in molecular research and chemical applications. They are natural cyclic oligosaccharides typically employed to encapsulate hydrophobic groups in their central cavity. This allows solubilizing, protecting or reducing the toxicity of a large variety of different molec...
Article
Full-text available
Motivation: Cyclodextrins (CDs) are amongst the most versatile/multi-functional molecules used in molecular research and chemical applications. They are natural cyclic oligosaccharides typically employed to encapsulate hydrophobic groups in their central cavity. This allows solubilizing, protecting or reducing the toxicity of a large variety of di...
Article
2-Alkenylphenols react with allenes, upon treatment with catalytic amounts of Pd(II) and Cu(II), to give benzoxepine products in high yields and with very good regio- and diastereoselectivities. This contrasts with the results obtained with Rh catalysts, which provided chromene-like products through a pathway involving a β-hydrogen elimination step...
Article
Full-text available
A macromolecular nanopore inserted into a membrane may perturb the dynamic organization of the surrounding lipid bilayer. To better understand the nature of such perturbations, we have undertaken a systematic molecular dynamics simulation study of lipid bilayer structure and dynamics around three different classes of nanopore: a carbon nanotube, th...
Article
Full-text available
We report the rational design of a DNA-binding peptide construct composed of the DNA-contacting regions of two transcription factors (GCN4 and GAGA) linked through an AT-hook DNA anchor. The resulting chimera, which represents a new, non-natural DNA binding motif, binds with high affinity and selectivity to a long composite sequence of 13 base pair...
Article
Full-text available
The design and synthesis of β-sheet-based self-assembling cyclic peptides with tunable cavities is described. The incorporation of a γ-amino acid with a hydroxyl group at C2 allows the incorporation of different groups that modify the internal properties of the resulting dimeric ensemble. These dimers can entrap different guests depending on the pr...
Article
A molecular dynamics study on internally functionalized peptide nanotubes composed of α- and γ-amino acids self-assembled in lipid bilayers is presented. One of the main advantages of peptide nanotubes composed of γ-amino acids is that the properties of their inner cavities can be tuned by introducing different functions on β-carbon of the γ-amino...
Article
Subnanometric noble metal clusters, composed by only a few atoms, behave like molecular entities and display magnetic, luminescent and catalytic activities. However, non-covalent interactions of molecular metal clusters, lacking of any ligand or surfactant, have not been seen at work. Theoretically attractive and experimentally discernable, van der...
Article
Full-text available
Peptide nanotubes are novel supramolecular nanobiomaterials that have a tubular structure. The stacking of cyclic components is one of the most promising strategies amongst the methods described in recent years for the preparation of nanotubes. This strategy allows precise control of the nanotube surface properties and the dimensions of the tube di...
Article
We describe the thermodynamic characterisation of the self-sorting process experienced by two homodimers assembled by hydrogen-bonding interactions through their cyclopeptide scaffolds and decorated with Zn-porphyrin and fullerene units into a heterodimeric assembly that contains one electron-donor (Zn-porphyrin) and one electron-acceptor group (fu...
Article
Alkyne tethered benzamides undergo rhodium(III)-catalyzed intramolecular annulations to give tricyclic isoquinoline derivatives in good yields. DFT calculations suggest that the reaction mechanism involves a migratory insertion of the alkyne into the rhodium–nitrogen bond of the rhodacycle intermediate that results from the initial C–H activation....
Article
We present here a molecular dynamics study on peptide nanotubes composed of cis-3-aminocyclohexanecarboxylic acid-(γ-Ach) or cis-3-aminocyclopentanecarboxylic acid (γ-Acp)-based α,γ-cyclohexapeptides and also on those formed by heterodimeric pairs from a combination of the two aforementioned peptides (γ-Ach/Acp), which is the first time that a self...
Article
In this study, we describe the self-assembling properties of cyclic peptides containing γ-amino acids in lipid bilayers to form transmembrane nanotubes. The resulting ion channel models are selective for alkaline ions. Although the transport rates conform to the lyotropic series, these partially hydrophobic channels show an unexpectedly higher rate...
Data
Distribution of different structural descriptors in the meta-trajectory of apoflavodoxin obtained at room temperature. TOP/LEFT: native and total contacts (referred to crystal contacts); TOP/RIGHT: solvent accessible surface (total, hydrophobic and hydrophilic, all in Å2); BOTTOM/LEFT: native contacts of structures in the three clusters; BOTTOM/RIG...
Data
Distribution of the Trp solvent accessible (in Å2) surface obtained descriptors in the meta-trajectory of apoflavodoxin obtained at room temperature. Reference values correspond to crystal, a highly distorted protein and four fully exposed Trp (see Figure 6 for details). (TIF)
Data
Distribution of the χ values (the fitting merit function) obtained when MD ensembles of apoflavodoxin at room temperature were used to fit SAXs experimental spectra. (TIF)
Data
Contact plots corresponding to the native and intermediate ensembles. Regions where loss of contacts are especially remarkable are marked. (TIF)
Data
Detail of the loop packing in the crystal lattice of two crystal structures of apoflavodoxin (1FTG, that used as reference here) and 1DX9 (which displays a different crystal symmetry). (TIF)
Data
Experimental ultraviolet spectra of native, unfolded and intermediate states of apoflavodoxin (see text for details). (TIF)
Article
Full-text available
The early stages of the thermal unfolding of apoflavodoxin have been determined by using atomistic multi microsecond-scale molecular dynamics (MD) simulations complemented with a variety of experimental techniques. Results strongly suggest that the intermediate is reached very early in the thermal unfolding process and that it has the properties of...
Article
The intramolecular (3 + 2) cycloaddition of alkenylidenecyclopropanes to alkenes under palladium catalysis provides a practical and stereoselective entry into a variety of interesting bicycles. The reaction outcome and stereoselectivity of the process are somewhat dependent on the characteristics of the substrate and of the palladium ligand, which...
Article
A practical protocol for the hydroalkynylation of enones using Pd catalysis is reported. The reaction proceeds efficiently with a variety of alkynes as well as with several cyclic and acyclic enones, providing synthetically relevant β-alkynyl ketones in good to excellent yields.
Article
Full-text available
Biomimetic nanopores based on membrane-spanning single-walled carbon nanotubes have been designed to include selectivity filters based on combinations of anionic and cationic groups mimicking those present in bacterial porins and in voltage-gated sodium and calcium channels. The ion permeation and selectivity properties of these nanopores when embe...
Chapter
In the last few years, interest on nanotubes have induced the development of programs for the preparation of noncovalently bonded self-organizing nanotubes from a variety of different methods, in most cases inspired by nature. These strategies include helically folded linear species, hollow bundles of rod-like units, rolled-up sheets, helically jux...
Article
The building blocks of a promising class of peptide nanotubes composed of alternating D-alpha-amino acids and (1R,3S)-3-aminocyclohexane (or cyclopentane) carboxylic acid (D-gamma-Ach or D-gamma-Acp) were explored by computational methods. Specifically, density functional theory (DFT) calculations on monomers and dimers of gamma-Ach-based and gamma...
Article
Here we describe a self-assembling alpha,gamma-cyclic tetrapeptide that contains the 4-amino-3-hydroxytetrahydrofuran-2-carboxylic acid, in which the hydroxy group is pointing towards the inner cavity of the resulting dimers.
Article
We present here a molecular dynamics study on a promising class of peptide nanotubes with a partially hydrophobic inner cavity and an easy chemical functionalization of the lumen of the cylindrical structure. The structural and dynamical behavior of the nanotube in water, methanol, and chloroform has been analyzed using state of the art theoretical...
Article
The mechanism of the palladium-catalysed [3+2] intramolecular cycloaddition of alkylidenecyclopropanes to alkynes has been computationally explored at DFT level. The energies of the reaction intermediates and transition states for different possible pathways have been calculated in a model system that involves the use of PH3 as a ligand. The result...
Article
The mechanism of enyne metathesis catalyzed by first and second generation Grubbs complexes has been computationally explored at the DFT level. The relative reactivity and the regioselectivity for the reaction of differently substituted alkenes and alkynes with model Ru complexes has been studied. The usually accepted dissociative mechanism for the...
Article
A cascade dienyne ring-closing metathesis approach has been applied to the synthesis of the tetracyclic carbon framework of a new class of hybrid compounds-the taxosteroids-possessing carbon frameworks incorporating moieties characteristic of both taxanes (such as AB rings) and steroids (i.e., CD system and side chain). This tandem cyclization is h...