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1.
Adv Healthc Mater ; 12(32): e2301527, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37826854

RESUMEN

Effective and accessible treatments for Alzheimer's disease (AD) are urgently needed. Soluble Aß oligomers are identified as neurotoxic species in AD and targeted in antibody-based drug development to mitigate cognitive decline. However, controversy exists concerning their efficacy and safety. In this study, an alternative strategy is proposed to inhibit the formation of Aß oligomers by selectively oxidizing specific amino acids in the Aß sequence, thereby preventing its aggregation. Targeted oxidation is achieved using biocompatible and blood-brain barrier-permeable multicomponent nanoscintillators that generate singlet oxygen upon X-ray interaction. Surface-modified scintillators interact selectively with Aß and, upon X-ray irradiation, inhibit the formation of neurotoxic aggregates both in vitro and in vivo. Feeding transgenic Caenorhabditis elegans expressing human Aß with the nanoscintillators and subsequent irradiation with soft X-ray reduces Aß oligomer levels, extends lifespan, and restores memory and behavioral deficits. These findings support the potential of X-ray-based therapy for AD and warrant further development.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/química , Barrera Hematoencefálica/metabolismo , Anticuerpos/metabolismo
2.
Proc Natl Acad Sci U S A ; 119(49): e2210766119, 2022 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-36442093

RESUMEN

Transient soluble oligomers of amyloid-ß (Aß) are toxic and accumulate early prior to insoluble plaque formation and cognitive impairment in Alzheimer's disease (AD). Synthetic cyclic D,L-α-peptides (e.g., 1) self-assemble into cross ß-sheet nanotubes, react with early Aß species (1-3 mers), and inhibit Aß aggregation and toxicity in stoichiometric concentrations, in vitro. Employing a semicarbazide as an aza-glycine residue with an extra hydrogen-bond donor to tune nanotube assembly and amyloid engagement, [azaGly6]-1 inhibited Aß aggregation and toxicity at substoichiometric concentrations. High-resolution NMR studies revealed dynamic interactions between [azaGly6]-1 and Aß42 residues F19 and F20, which are pivotal for early dimerization and aggregation. In an AD mouse model, brain positron emission tomography (PET) imaging using stable 64Cu-labeled (aza)peptide tracers gave unprecedented early amyloid detection in 44-d presymptomatic animals. No tracer accumulation was detected in the cortex and hippocampus of 44-d-old 5xFAD mice; instead, intense PET signal was observed in the thalamus, from where Aß oligomers may spread to other brain parts with disease progression. Compared with standard 11C-labeled Pittsburgh compound-B (11C-PIB), which binds specifically fibrillar Aß plaques, 64Cu-labeled (aza)peptide gave superior contrast and uptake in young mouse brain correlating with Aß oligomer levels. Effectively crossing the blood-brain barrier (BBB), peptide 1 and [azaGly6]-1 reduced Aß oligomer levels, prolonged lifespan of AD transgenic Caenorhabditis elegans, and abated memory and behavioral deficits in nematode and murine AD models. Cyclic (aza)peptides offer novel promise for early AD diagnosis and therapy.


Asunto(s)
Enfermedad de Alzheimer , Amiloidosis , Animales , Ratones , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/tratamiento farmacológico , Diagnóstico Precoz , Péptidos beta-Amiloides , Placa Amiloide , Proteínas Amiloidogénicas
3.
Phys Chem Chem Phys ; 24(11): 6699-6715, 2022 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-35234757

RESUMEN

In a wide spectrum of neurodegenerative diseases, self-assembly of pathogenic proteins to cytotoxic intermediates is accelerated by the presence of metal ions such as Cu2+. Only low concentrations of these early transient oligomeric intermediates are present in a mixture of species during fibril formation, and hence information on the extent of structuring of these oligomers is still largely unknown. Here, we investigate dimers as the first intermediates in the Cu2+-driven aggregation of a cyclic D,L-α-peptide architecture. The unique structural and functional properties of this model system recapitulate the self-assembling properties of amyloidogenic proteins including ß-sheet conformation and cross-interaction with pathogenic amyloids. We show that a histidine-rich cyclic D,L-α-octapeptide binds Cu2+ with high affinity and selectivity to generate amyloid-like cross-ß-sheet structures. By taking advantage of backbone amide methylation to arrest the self-assembly at the dimeric stage, we obtain structural information and characterize the degree of local order for the dimer. We found that, while catalytic amounts of Cu2+ promote aggregation of the peptide to fibrillar structures, higher concentrations dose-dependently reduce fibrillization and lead to formation of spherical particles, showing self-assembly to different polymorphs. For the initial self-assembly step to the dimers, we found that Cu2+ is coordinated on average by two histidines, similar to self-assembled peptides, indicating that a similar binding interface is perpetuated during Cu2+-driven oligomerization. The dimer itself is found in heterogeneous conformations that undergo dynamic exchange, leading to the formation of different polymorphs at the initial stage of the aggregation process.


Asunto(s)
Amiloide , Enfermedades Neurodegenerativas , Péptidos Cíclicos , Amiloide/biosíntesis , Amiloide/química , Péptidos beta-Amiloides/química , Péptidos beta-Amiloides/metabolismo , Proteínas Amiloidogénicas/química , Proteínas Amiloidogénicas/metabolismo , Humanos , Enfermedades Neurodegenerativas/metabolismo , Péptidos Cíclicos/química , Péptidos Cíclicos/metabolismo , Conformación Proteica en Lámina beta
4.
Small ; 15(45): e1904203, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31482695

RESUMEN

Nerve growth factor (NGF) plays a vital role in reducing the loss of cholinergic neurons in Alzheimer's disease (AD). However, its delivery to the brain remains a challenge. Herein, NGF is loaded into degradable oxidized porous silicon (PSiO2 ) carriers, which are designed to carry and continuously release the protein over a 1 month period. The released NGF exhibits a substantial neuroprotective effect in differentiated rat pheochromocytoma PC12 cells against amyloid-beta (Aß)-induced cytotoxicity, which is associated with Alzheimer's disease. Next, two potential localized administration routes of the porous carriers into murine brain are investigated: implantation of PSiO2 chips above the dura mater, and biolistic bombardment of PSiO2 microparticles through an opening in the skull using a pneumatic gene gun. The PSiO2 -implanted mice are monitored for a period of 8 weeks and no inflammation or adverse effects are observed. Subsequently, a successful biolistic delivery of these highly porous microparticles into a live-mouse brain is demonstrated for the first time. The bombarded microparticles are observed to penetrate the brain and reach a depth of 150 µm. These results pave the way for using degradable PSiO2 carriers as potential localized delivery systems for NGF to the brain.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Nanoestructuras/química , Factor de Crecimiento Nervioso/química , Factor de Crecimiento Nervioso/uso terapéutico , Silicio/química , Animales , Supervivencia Celular/efectos de los fármacos , Ratones , Microscopía Confocal , Microscopía Fluorescente , Nanoestructuras/uso terapéutico , Factor de Crecimiento Nervioso/farmacocinética , Células PC12 , Porosidad , Ratas , Microtomografía por Rayos X
5.
Chem Sci ; 10(1): 208-217, 2019 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-30713632

RESUMEN

The self-assembly of Aß to ß-sheet-rich neurotoxic oligomers is a main pathological event leading to Alzheimer's disease (AD). Selective targeting of Aß oligomers without affecting other functional proteins is therefore an attractive approach to prevent the disease and its progression. In this study, we report that photodynamic treatment of Aß in the presence of catalytic amounts of chlorin e6 can selectively damage Aß and inhibit its aggregation and toxicity. Chlorin e6 also reversed the amyloid aggregation process in the dark by binding its soluble and low molecular weight oligomers, as shown by thioflavin T (ThT) fluorescence and photoinduced cross-linking of unmodified protein (PICUP) methods. Using HSQC NMR spectroscopy, ThT assays, amino acid analysis, SDS/PAGE, and EPR spectroscopy, we show that catalytic amounts of photoexcited chlorin e6 selectively damage the Aß histidine residues H6, H13, and H14, and induce Aß cross-linking by generating singlet oxygen. In contrast, photoexcited chlorin e6 was unable to cross-link ubiquitin and α-synuclein, demonstrating its high selectivity for Aß. By binding to the Aß histidine residues, catalytic amounts of chlorin e6 can also inhibit the Cu2+-induced aggregation and toxicity in darkness, while at stoichiometric amounts it acts as a chelator to reduce the amount of free Cu2+. This study demonstrates the great potential of chlorin e6 as a multifunctional agent for treatment of AD, and shows that the three N-terminal Aß histidine residues are a suitable target for Aß-specific drugs.

6.
Chemistry ; 24(53): 14039-14043, 2018 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-30144161

RESUMEN

Protein phosphorylation and O-GlcNAcylation are very common nucleoplasmic post-translational modifications. Mono-addition of either the phosphate or the O-GlcNAc group were shown to inhibit the self-aggregation of amyloidogenic proteins and peptides, which is the hallmark of various protein misfolding diseases. However, their comparable effect upon co-incubation with a native non-modified amyloid scaffold has not been reported. O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide. These results shed light on the role of post-translational modifications in protein aggregation and suggest a novel therapeutic approach to protein misfolding diseases.

7.
Chemistry ; 22(40): 14236-46, 2016 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-27539220

RESUMEN

Many peptides and proteins with large sequences and structural differences self-assemble into disease-causing amyloids that share very similar biochemical and biophysical characteristics, which may contribute to their cross-interaction. Here, we demonstrate how the self-assembled, cyclic d,l-α-peptide CP-2, which has similar structural and functional properties to those of amyloids, acts as a generic inhibitor of the Parkinson's disease associated α-synuclein (α-syn) aggregation to toxic oligomers by an "off-pathway" mechanism. We show that CP-2 interacts with the N-terminal and the non-amyloid-ß component region of α-syn, which are responsible for α-syn's membrane intercalation and self-assembly, thus changing the overall conformation of α-syn. CP-2 also remodels α-syn fibrils to nontoxic amorphous species and permeates cells through endosomes/lysosomes to reduce the accumulation and toxicity of intracellular α-syn in neuronal cells overexpressing α-syn. Our studies suggest that targeting the common structural conformation of amyloids may be a promising approach for developing new therapeutics for amyloidogenic diseases.


Asunto(s)
Enfermedad de Parkinson/tratamiento farmacológico , Péptidos Cíclicos/farmacología , Agregado de Proteínas/efectos de los fármacos , Agregación Patológica de Proteínas/tratamiento farmacológico , alfa-Sinucleína/metabolismo , Amiloide/metabolismo , Amiloide/ultraestructura , Animales , Humanos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Células PC12 , Enfermedad de Parkinson/metabolismo , Péptidos Cíclicos/química , Péptidos Cíclicos/farmacocinética , Agregación Patológica de Proteínas/metabolismo , Ratas , alfa-Sinucleína/ultraestructura
8.
Chemistry ; 22(17): 5945-52, 2016 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-26891276

RESUMEN

Protein glycosylation is a ubiquitous post-translational modification that regulates the folding and function of many proteins. Misfolding of protein monomers and their toxic aggregation are the hallmark of many prevalent diseases. Thus, understanding the role of glycans in protein aggregation is highly important and could contribute both to unraveling the pathology of protein misfolding diseases as well as providing a means for modifying their course for therapeutic purposes. Using ß-O-linked glycosylated variants of the highly studied Tau-derived hexapeptide motif VQIVYK, which served as a simplified amyloid model, we demonstrate that amyloid formation and toxicity can be strongly attenuated by a glycan unit, depending on the nature of the glycan itself. Importantly, we show for the first time that not only do glycans hinder self-aggregation, but the glycosylated peptides are capable of inhibiting aggregation of the non-modified corresponding amyloid scaffold.


Asunto(s)
Amiloide/antagonistas & inhibidores , Amiloide/química , Oligopéptidos/química , Péptidos/química , Proteínas tau/química , Secuencia de Aminoácidos , Amiloide/metabolismo , Glicosilación , Humanos , Oligopéptidos/metabolismo , Péptidos/metabolismo , Procesamiento Proteico-Postraduccional , Estructura Secundaria de Proteína , Proteínas tau/metabolismo
9.
Chem Commun (Camb) ; 52(11): 2350-3, 2016 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-26731129

RESUMEN

The phenol-diamide compound, 5-(tert-butyl)-2-hydroxy-N1,N3-bis(2-hydroxyethyl)isophthalamide (), is water-soluble, non-cytotoxic, and capable of both, trapping ROS species and chelating Cu(ii) and Fe(iii) ions; these combined properties confer a protective effect against ROS induced cell death.


Asunto(s)
Quelantes/química , Depuradores de Radicales Libres/química , Agua/química , Solubilidad
10.
J Med Chem ; 56(17): 6709-18, 2013 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-23984871

RESUMEN

Oxidative stress directly correlates with the early onset of vascular complications and the progression of peripheral insulin resistance in diabetes. Accordingly, exogenous antioxidants augment insulin sensitivity in type 2 diabetic patients and ameliorate its clinical signs. Herein, we explored the unique structural and functional properties of the abiotic cyclic D,L-α-peptide architecture as a new scaffold for developing multifunctional agents to catalytically decompose ROS and stimulate glucose uptake. We showed that His-rich cyclic D,L-α-peptide 1 is very stable under high H2O2 concentrations, effectively self-assembles to peptide nanotubes, and increases the uptake of glucose by increasing the translocation of GLUT1 and GLUT4. It also penetrates cells and protects them against oxidative stress induced under hyperglycemic conditions at a much lower concentration than α-lipoic acid (ALA). In vivo studies are now required to probe the mode of action and efficacy of these abiotic cyclic D,L-α-peptides as a novel class of antihyperglycemic compounds.


Asunto(s)
Glucosa/metabolismo , Insulina/metabolismo , Músculo Esquelético/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Péptidos Cíclicos/farmacología , Animales , Línea Celular , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 4/metabolismo , Ratones , Microscopía Electrónica de Transmisión , Músculo Esquelético/citología , Músculo Esquelético/metabolismo , Péptidos Cíclicos/química , Conformación Proteica
11.
Chem Commun (Camb) ; 49(51): 5721-3, 2013 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-23364289

RESUMEN

A facile, versatile, and one-pot sonochemical synthesis of polydopamine (PDA)-nanocapsules from dopamine is reported. The nanocapsules (227 ± 25 nm) can encapsulate hydrophobic substances while retaining the reactivity of PDA toward nucleophilic reactions, enabling facile surface modification for different applications. PDA nanocapsules are nontoxic to mammalian cells while Cu-containing PDA capsules demonstrate strong (99.9%) and rapid (15 min) bactericidal activity.


Asunto(s)
Antibacterianos/química , Indoles/química , Nanocápsulas/química , Polímeros/química , Animales , Antibacterianos/farmacología , Antibacterianos/toxicidad , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Sulfato de Cobre/química , Nanocápsulas/toxicidad , Pseudomonas aeruginosa/efectos de los fármacos , Ratas , Staphylococcus aureus/efectos de los fármacos , Ultrasonido
12.
J Am Chem Soc ; 135(9): 3474-84, 2013 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-23360549

RESUMEN

Misfolding of the Aß protein and its subsequent aggregation into toxic oligomers are related to Alzheimer's disease. Although peptides of various sequences can self-assemble into amyloid structures, these structures share common three-dimensional features that may promote their cross-reaction. Given the significant similarities between amyloids and the architecture of self-assembled cyclic D,L-α-peptide, we hypothesized that the latter may bind and stabilize a nontoxic form of Aß, thereby preventing its aggregation into toxic forms. By screening a focused library of six-residue cyclic D,L-α-peptides and optimizing the activity of a lead peptide, we found one cyclic D,L-α-peptide (CP-2) that interacts strongly with Aß and inhibits its aggregation. In transmission electron microscopy, optimized thioflavin T and cell survival assays, CP-2 inhibits the formation of Aß aggregates, entirely disassembles preformed aggregated and fibrillar Aß, and protects rat pheochromocytoma PC12 cells from Aß toxicity, without inducing any toxicity by itself. Using various immunoassays, circular dichroism spectroscopy, photoinduced cross-linking of unmodified proteins (PICUP) combined with SDS/PAGE, and NMR, we probed the mechanisms underlying CP-2's antiamyloidogenic activity. NMR spectroscopy indicates that CP-2 interacts with Aß through its self-assembled conformation and induces weak secondary structure in Aß. Upon coincubation, CP-2 changes the aggregation pathway of Aß and alters its oligomer distribution by stabilizing small oligomers (1-3 mers). Our results support studies suggesting that toxic early oligomeric states of Aß may be composed of antiparallel ß-peptide structures and that the interaction of Aß with CP-2 promotes formation of more benign parallel ß-structures. Further studies will show whether these kinds of abiotic cyclic D,L-α-peptides are also beneficial as an intervention in related in vivo models.


Asunto(s)
Péptidos beta-Amiloides/antagonistas & inhibidores , Péptidos Cíclicos/farmacología , Péptidos beta-Amiloides/síntesis química , Péptidos beta-Amiloides/química , Animales , Células Cultivadas , Células PC12 , Péptidos Cíclicos/síntesis química , Péptidos Cíclicos/química , Conformación Proteica , Ratas
13.
Biomacromolecules ; 14(1): 110-6, 2013 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-23163430

RESUMEN

Imbalanced homeostasis and oligomerization of the amyloid-ß (Aß) peptide in the brain are hallmarks of Alzheimer's disease (AD). Microglia and macrophages play a critical role in the etiology of AD either by clearing Aß from the brain or inducing inflammation. Recent evidence suggests that clearance of Aß by microglia/macrophages via the phagocytic pathway is defective in AD, which can contribute to the accumulation of Aß in the brain. We have recently demonstrated that protein microspheres modified at their surface with multiple copies of an Aß-recognition motif can strongly bind Aß, inhibit its aggregation, and directly reduce its toxicity by sequestering it from the medium. Here, we describe how microsphere-bound Aß can stimulate microglial cells and be phagocytosed through a mechanism that is distinct from that of Aß removal and, thus, contribute to the clearance of Aß, even by defective microglial cells. The phagocytosis was most effective, with microspheres having a diameter of <1 µm. The introduction of polyethylene glycol to the surface of the microspheres changed the kinetics of the phagocytosis. Moreover, while aggregated Aß induced a significant inflammatory response that was manifested by the release of TNF-α, the microsphere-bound Aß dramatically reduced the amount of cytokine released from microglial cells.


Asunto(s)
Péptidos beta-Amiloides/administración & dosificación , Péptidos beta-Amiloides/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Macrófagos/metabolismo , Microesferas , Albúmina Sérica Bovina/metabolismo , Animales , Bovinos , Línea Celular , Células Cultivadas , Humanos , Macrófagos/efectos de los fármacos , Ratones , Microglía/química , Microglía/metabolismo , Fagocitosis/fisiología , Albúmina Sérica Bovina/química , Propiedades de Superficie
14.
Chem Commun (Camb) ; 48(67): 8359-61, 2012 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-22798998

RESUMEN

A novel application of surface-modified protein nanospheres as potential antiviral agents is illustrated. By using a single-step sonochemical process, bovine serum albumin nanospheres were generated, whose surface was covalently conjugated with mercaptoethane sulfonate to chemically and electrostatically mimic cellular heparan sulfate. The nanospheres effectively inhibited HSV-1 infection.


Asunto(s)
Antivirales/química , Nanosferas/química , Albúmina Sérica Bovina/química , Animales , Antivirales/farmacología , Bovinos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Herpesvirus Humano 1/efectos de los fármacos , Mercaptoetanol/química , Ácidos Sulfónicos/química , Propiedades de Superficie
15.
Chemistry ; 17(40): 11171-7, 2011 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-21887833

RESUMEN

The biocompatible and biodegradable properties of protein microspheres and the recent advances in their preparation have generated considerable interest of utilizing these core-shell structures for drug delivery and diagnostic applications. However, effective targeting of protein microspheres to desirable cells or loci still remains a challenge. Here, we describe for the first time a facile one-pot sonochemical approach for covalent modification of protein microspheres made from serum albumin; the surface of which is covalently decorated with a short recognition peptide to target amyloid-ß (Aß) as the main pathogenic protein in Alzheimer's disease (AD). The microspheres were characterized for their morphology, size, and entrapment efficacy by electron microscopy, dynamic light scattering and confocal microscopy. Fluorescence-activated cell-sorting analysis and Thioflavin-T binding assay demonstrated that the conjugated microspheres bind with high affinity and selectivity to Aß, sequester it from the medium and reduce its aggregation. Upon incubation with Aß, the microspheres induced formation of amorphous aggregates on their surface with no apparent fibrillar structure. Moreover, the microspheres directly reduced the Aß-induced toxicity toward neuron like PC12 cells. The conjugated microspheres are smaller than unmodified microspheres and remained stable throughout the incubation under physiological conditions.


Asunto(s)
Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/química , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/toxicidad , Fragmentos de Péptidos/química , Fragmentos de Péptidos/metabolismo , Fragmentos de Péptidos/toxicidad , Péptidos/química , Péptidos/metabolismo , Péptidos/toxicidad , Albúmina Sérica Bovina/química , Animales , Sistemas de Liberación de Medicamentos , Humanos , Microscopía Electrónica , Microesferas , Unión Proteica , Ratas
16.
Chem Commun (Camb) ; 47(45): 12277-9, 2011 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-21858303

RESUMEN

We report a remarkably facile one-pot sonochemical approach to prepare protein microspheres whose shells are covalently decorated with a mannosyl derivative to target Escherichia coli (E. coli), while their cores are encapsulated with tetracycline. Conjugated microspheres induced the agglutination of E. coli and increased the anti-bacterial activity of the encapsulated tetracycline by five fold.


Asunto(s)
Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Manosa/química , Proteínas/química , Tetraciclina/farmacología , Animales , Bovinos , Disulfuros/química , Escherichia coli/efectos de los fármacos , Albúmina Sérica Bovina/química
17.
Chem Phys Lipids ; 155(2): 98-113, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18675263

RESUMEN

The development of "molecular rulers" would allow one to quantitatively locate intercalants within the liposomal bilayer. To this end, we have attempted to correlate the 13C NMR chemical shift of a polarizable "reporter" carbon (e.g., carbonyl) of the intercalant-with the ET30 polarity it experiences, and with its Angstrom distance from the interface. This requires families of molecules with the same two "reporter carbons" separated by a fixed distance, residing at various depths/polarities within the bilayer. The families studied included 4,4-dialkylcyclohexa-2,5-dienones 1, benzenediacetic esters 15, benzenedipropionic esters 17, 4-alkoxybenzaldehydes 19 and methyl 4-alkoxybenzoates 22. These compounds possessed the following characteristics: (1) a planar backbone; (2) polar/hydrophilic "head" groups; (3) modular hydrophobic tails; (4) large changes in the 13C NMR chemical shift (Deltadelta) of the reporter atoms with solvent polarity. These studies revealed a fifth requirement, namely: (5) the reporter carbons must not be strongly conjugated, lest it reflect the charge build-up at another site within the conjugated system.


Asunto(s)
Membrana Dobles de Lípidos/química , Espectroscopía de Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética/normas , Benzaldehídos/análisis , Benzaldehídos/química , Benzoatos/análisis , Benzoatos/síntesis química , Benzoatos/química , Ciclohexenos/análisis , Ciclohexenos/síntesis química , Ciclohexenos/química , Dimiristoilfosfatidilcolina/química , Ésteres/análisis , Ésteres/síntesis química , Ésteres/química , Liposomas/química
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