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1.
J Am Chem Soc ; 145(32): 17497-17514, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37535757

RESUMO

meso-methyl BODIPY photocages have recently emerged as an exciting new class of photoremovable protecting groups (PPGs) that release leaving groups upon absorption of visible to near-infrared light. In this Perspective, we summarize the development of these PPGs and highlight their critical photochemical properties and applications. We discuss the absorption properties of the BODIPY PPGs, structure-photoreactivity studies, insights into the photoreaction mechanism, the scope of functional groups that can be caged, the chemical synthesis of these structures, and how substituents can alter the water solubility of the PPG and direct the PPG into specific subcellular compartments. Applications that exploit the unique optical and photochemical properties of BODIPY PPGs are also discussed, from wavelength-selective photoactivation to biological studies to photoresponsive organic materials and photomedicine.

2.
Chem Rev ; 120(24): 13135-13272, 2020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33125209

RESUMO

Photoactivatable (alternatively, photoremovable, photoreleasable, or photocleavable) protecting groups (PPGs), also known as caged or photocaged compounds, are used to enable non-invasive spatiotemporal photochemical control over the release of species of interest. Recent years have seen the development of PPGs activatable by biologically and chemically benign visible and near-infrared (NIR) light. These long-wavelength-absorbing moieties expand the applicability of this powerful method and its accessibility to non-specialist users. This review comprehensively covers organic and transition metal-containing photoactivatable compounds (complexes) that absorb in the visible- and NIR-range to release various leaving groups and gasotransmitters (carbon monoxide, nitric oxide, and hydrogen sulfide). The text also covers visible- and NIR-light-induced photosensitized release using molecular sensitizers, quantum dots, and upconversion and second-harmonic nanoparticles, as well as release via photodynamic (photooxygenation by singlet oxygen) and photothermal effects. Release from photoactivatable polymers, micelles, vesicles, and photoswitches, along with the related emerging field of photopharmacology, is discussed at the end of the review.

3.
J Am Chem Soc ; 142(11): 4970-4974, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32115942

RESUMO

Photoactivation of bioactive molecules allows manipulation of cellular processes with high spatiotemporal precision. The recent emergence of visible-light excitable photoprotecting groups has the potential to further expand the established utility of the photoactivation strategy in biological applications by offering higher tissue penetration, diminished phototoxicity, and compatibility with other light-dependent techniques. Nevertheless, a critical barrier to such applications remains the significant hydrophobicity of most visible-light excitable photocaging groups. Here, we find that applying the conventional 2,6-sulfonation to meso-methyl BODIPY photocages is incompatible with their photoreaction due to an increase in the excited state barrier for photorelease. We present a simple, remote sulfonation solution to BODIPY photocages that imparts water solubility and provides control over cellular permeability while retaining their favorable spectroscopic and photoreaction properties. Peripherally disulfonated BODIPY photocages are cell impermeable, making them useful for modulation of cell-surface receptors, while monosulfonated BODIPY retains the ability to cross the cellular membrane and can modulate intracellular targets. This new approach is generalizable for controlling BODIPY localization and was validated by sensitization of mammalian cells and neurons by visible-light photoactivation of signaling molecules.


Assuntos
Alcanossulfonatos/metabolismo , Compostos de Boro/metabolismo , Corantes Fluorescentes/metabolismo , Alcanossulfonatos/síntese química , Alcanossulfonatos/efeitos da radiação , Animais , Compostos de Boro/síntese química , Compostos de Boro/efeitos da radiação , Membrana Celular/metabolismo , Dopamina/química , Dopamina/farmacologia , Portadores de Fármacos/síntese química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/efeitos da radiação , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Células HEK293 , Hipocampo/efeitos dos fármacos , Histamina/química , Histamina/farmacologia , Humanos , Luz , Microscopia Confocal , Microscopia de Fluorescência , Estrutura Molecular , Neurônios/efeitos dos fármacos , Ratos , Solubilidade
4.
Angew Chem Int Ed Engl ; 58(14): 4659-4663, 2019 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-30731033

RESUMO

Photocaging facilitates non-invasive and precise spatio-temporal control over the release of biologically relevant small- and macro-molecules using light. However, sub-cellular organelles are dispersed in cells in a manner that renders selective light-irradiation of a complete organelle impractical. Organelle-specific photocages could provide a powerful method for releasing bioactive molecules in sub-cellular locations. Herein, we report a general post-synthetic method for the chemical functionalization and further conjugation of meso-methyl BODIPY photocages and the synthesis of endoplasmic reticulum (ER)-, lysosome-, and mitochondria-targeted derivatives. We also demonstrate that 2,4-dinitrophenol, a mitochondrial uncoupler, and puromycin, a protein biosynthesis inhibitor, can be selectively photoreleased in mitochondria and ER, respectively, in live cells by using visible light. Additionally, photocaging is shown to lead to higher efficacy of the released molecules, probably owing to a localized and abrupt release.


Assuntos
Compostos de Boro/metabolismo , Luz , Organelas/metabolismo , Compostos de Boro/química , Retículo Endoplasmático/química , Retículo Endoplasmático/metabolismo , Células HeLa , Humanos , Mitocôndrias/química , Mitocôndrias/metabolismo , Estrutura Molecular , Organelas/química , Processos Fotoquímicos
5.
Dig Dis Sci ; 63(12): 3382-3397, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30196390

RESUMO

BACKGROUND AND AIMS: Concanavalin A is known to activate T cells and to cause liver injury and hepatitis, mediated in part by secretion of TNFα from macrophages. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors have been shown to prevent tissue damage in various animal models of inflammation. The objectives of this study were to evaluate the efficacy and mechanism of the PARP-1 inhibitor 3-aminobenzamide (3-AB) in preventing concanavalin A-induced liver damage. METHODS: We tested the in vivo effects of 3-AB on concanavalin A-treated mice, its effects on lipopolysaccharide (LPS)-stimulated macrophages in culture, and its ability to act as a scavenger in in vitro assays. RESULTS: 3-AB markedly reduced inflammation, oxidative stress, and liver tissue damage in concanavalin A-treated mice. In LPS-stimulated RAW264.7 macrophages, 3-AB inhibited NFκB transcriptional activity and subsequent expression of TNFα and iNOS and blocked NO production. In vitro, 3-AB acted as a hydrogen peroxide scavenger. The ROS scavenger N-acetylcysteine (NAC) and the ROS formation inhibitor diphenyleneiodonium (DPI) also inhibited TNFα expression in stimulated macrophages, but unlike 3-AB, NAC and DPI were unable to abolish NFκB activity. PARP-1 knockout failed to affect NFκB and TNFα suppression by 3-AB in stimulated macrophages. CONCLUSIONS: Our results suggest that 3-AB has a therapeutic effect on concanavalin A-induced liver injury by inhibiting expression of the key pro-inflammatory cytokine TNFα, via PARP-1-independent NFκB suppression and via an NFκB-independent anti-oxidative mechanism.


Assuntos
Benzamidas/farmacologia , Hepatite , Macrófagos , Doença Aguda , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Células Cultivadas , Concanavalina A/farmacologia , Modelos Animais de Doenças , Hepatite/metabolismo , Hepatite/prevenção & controle , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Camundongos , Mitógenos/farmacologia , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/metabolismo
6.
J Am Chem Soc ; 139(42): 15168-15175, 2017 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-29039200

RESUMO

A detailed investigation of the photophysical parameters and photochemical reactivity of meso-methyl BODIPY photoremovable protecting groups was accomplished through systematic variation of the leaving group (LG) and core substituents as well as substitutions at boron. Efficiencies of the LG release were evaluated using both steady-state and transient absorption spectroscopies as well as computational analyses to identify the optimal structural features. We find that the quantum yields for photorelease with this photocage are highly sensitive to substituent effects. In particular, we find that the quantum yields of photorelease are improved with derivatives with higher intersystem crossing quantum yields, which can be promoted by core heavy atoms. Moreover, release quantum yields are dramatically improved by boron alkylation, whereas alkylation in the meso-methyl position has no effect. Better LGs are released considerably more efficiently than poorer LGs. We find that these substituent effects are additive, for example, a 2,6-diiodo-B-dimethyl BODIPY photocage features quantum yields of 28% for the mediocre LG acetate and a 95% quantum yield of release for chloride. The high chemical and quantum yields combined with the outstanding absorption properties of BODIPY dyes lead to photocages with uncaging cross sections over 10 000 M-1 cm-1, values that surpass cross sections of related photocages absorbing visible light. These new photocages, which absorb strongly near the second harmonic of an Nd:YAG laser (532 nm), hold promise for manipulating and interrogating biological and material systems with the high spatiotemporal control provided by pulsed laser irradiation, while avoiding the phototoxicity problems encountered with many UV-absorbing photocages. More generally, the insights gained from this structure-reactivity relationship may aid in the development of new highly efficient photoreactions.

7.
Plant Physiol ; 170(3): 1624-39, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26802039

RESUMO

Plant trichomes are defensive specialized epidermal cells. In all accepted models, the epidermis is the layer involved in trichome formation, a process controlled by gibberellins (GAs) in Arabidopsis rosette leaves. Indeed, GA activates a genetic cascade in the epidermis for trichome initiation. Here we report that TEMPRANILLO (TEM) genes negatively control trichome initiation not only from the epidermis but also from the leaf layer underneath the epidermis, the mesophyll. Plants over-expressing or reducing TEM specifically in the mesophyll, display lower or higher trichome numbers, respectively. We surprisingly found that fluorescently labeled GA3 accumulates exclusively in the mesophyll of leaves, but not in the epidermis, and that TEM reduces its accumulation and the expression of several newly identified GA transporters. This strongly suggests that TEM plays an essential role, not only in GA biosynthesis, but also in regulating GA distribution in the mesophyll, which in turn directs epidermal trichome formation. Moreover, we show that TEM also acts as a link between GA and cytokinin signaling in the epidermis by negatively regulating downstream genes of both trichome formation pathways. Overall, these results call for a re-evaluation of the present theories of trichome formation as they reveal mesophyll essential during epidermal trichome initiation.


Assuntos
Proteínas de Arabidopsis/metabolismo , Epiderme Vegetal/metabolismo , Folhas de Planta/metabolismo , Fatores de Transcrição/metabolismo , Tricomas/metabolismo , Arabidopsis/citologia , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Citocininas/metabolismo , Regulação da Expressão Gênica de Plantas , Giberelinas/metabolismo , Inflorescência/citologia , Inflorescência/genética , Inflorescência/metabolismo , Microscopia Eletrônica de Varredura , Mutação , Epiderme Vegetal/citologia , Epiderme Vegetal/genética , Folhas de Planta/citologia , Folhas de Planta/genética , Plantas Geneticamente Modificadas , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Fatores de Transcrição/genética , Tricomas/genética , Tricomas/ultraestrutura
8.
J Exp Bot ; 67(18): 5495-5508, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27580624

RESUMO

The potato tuber is a swollen underground stem that can sprout under dark conditions. Sprouting initiates in the tuber apical bud (AP), while lateral buds (LTs) are repressed by apical dominance (AD). Under conditions of lost AD, removal of tuber LTs showed that they partially inhibit AP growth only at the AD stage. Detached buds were inhibited by exogenous application of naphthaleneacetic acid (NAA), whereas 6-benzyladenine (6-BA) and gibberellic acid (GA3) induced bud burst and elongation, respectively. NAA, applied after 6-BA or GA3, nullified the latters' growth-stimulating effect in both the AP and LTs. GA3 applied to the fifth-position LT was transported mainly to the tuber's AP. GA3 treatment also resulted in increased indole-3-acetic acid (IAA) concentration and cis-zeatin O-glucoside in the AP. In a tuber tissue strip that included two or three buds connected by the peripheral vascular system, treatment of a LT with GA3 affected only the AP side of the strip, suggesting that the AP is the strongest sink for GA3, which induces its etiolated elongation. Dipping etiolated sprouts in labeled GA3 showed specific accumulation of the signal in the AP. Transcriptome analysis of GA3's effect showed that genes related to the cell cycle, cell proliferation, and hormone transport are up-regulated in the AP as compared to the LT. Sink demand for metabolites is suggested to support AD in etiolated stem growth by inducing differential gene expression in the AP.


Assuntos
Tubérculos/metabolismo , Solanum tuberosum/metabolismo , Compostos de Benzil/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/fisiologia , Giberelinas/farmacologia , Glucosídeos/metabolismo , Ácidos Indolacéticos/metabolismo , Ácidos Naftalenoacéticos/farmacologia , Reguladores de Crescimento de Plantas/farmacologia , Tubérculos/efeitos dos fármacos , Tubérculos/crescimento & desenvolvimento , Purinas/farmacologia , Solanum tuberosum/efeitos dos fármacos , Solanum tuberosum/crescimento & desenvolvimento
9.
Proc Natl Acad Sci U S A ; 110(12): 4834-9, 2013 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-23382232

RESUMO

Plant hormones are small-molecule signaling compounds that are collectively involved in all aspects of plant growth and development. Unlike animals, plants actively regulate the spatial distribution of several of their hormones. For example, auxin transport results in the formation of auxin maxima that have a key role in developmental patterning. However, the spatial distribution of the other plant hormones, including gibberellic acid (GA), is largely unknown. To address this, we generated two bioactive fluorescent GA compounds and studied their distribution in Arabidopsis thaliana roots. The labeled GAs specifically accumulated in the endodermal cells of the root elongation zone. Pharmacological studies, along with examination of mutants affected in endodermal specification, indicate that GA accumulation is an active and highly regulated process. Our results strongly suggest the presence of an active GA transport mechanism that would represent an additional level of GA regulation.


Assuntos
Arabidopsis/fisiologia , Giberelinas/metabolismo , Raízes de Plantas/metabolismo , Arabidopsis/citologia , Transporte Biológico Ativo/fisiologia , Ácidos Indolacéticos/metabolismo , Raízes de Plantas/citologia
10.
J Am Chem Soc ; 136(3): 874-7, 2014 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-24377760

RESUMO

A hydrogen peroxide (H2O2)-activated cell-penetrating peptide was developed through incorporation of a boronic acid-containing cleavable linker between polycationic cell-penetrating peptide and polyanionic fragments. Fluorescence labeling of the two ends of the molecule enabled monitoring its reaction with H2O2 through release of the highly adhesive cell-penetrating peptide and disruption of fluorescence resonance energy transfer. The H2O2 sensor selectively reacts with endogenous H2O2 in cell culture to monitor the oxidative burst of promyelocytes and in vivo to image lung inflammation. Targeting H2O2 has potential applications in imaging and therapy of diseases related to oxidative stress.


Assuntos
Técnicas Biossensoriais/métodos , Peptídeos Penetradores de Células/metabolismo , Peróxido de Hidrogênio/metabolismo , Ácidos Borônicos/química , Ácidos Borônicos/metabolismo , Sobrevivência Celular , Células HL-60 , Humanos , Imagem Molecular
11.
Nat Commun ; 15(1): 3895, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719832

RESUMO

Growth at the shoot apical meristem (SAM) is essential for shoot architecture construction. The phytohormones gibberellins (GA) play a pivotal role in coordinating plant growth, but their role in the SAM remains mostly unknown. Here, we developed a ratiometric GA signaling biosensor by engineering one of the DELLA proteins, to suppress its master regulatory function in GA transcriptional responses while preserving its degradation upon GA sensing. We demonstrate that this degradation-based biosensor accurately reports on cellular changes in GA levels and perception during development. We used this biosensor to map GA signaling activity in the SAM. We show that high GA signaling is found primarily in cells located between organ primordia that are the precursors of internodes. By gain- and loss-of-function approaches, we further demonstrate that GAs regulate cell division plane orientation to establish the typical cellular organization of internodes, thus contributing to internode specification in the SAM.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Técnicas Biossensoriais , Regulação da Expressão Gênica de Plantas , Giberelinas , Meristema , Transdução de Sinais , Giberelinas/metabolismo , Meristema/metabolismo , Meristema/crescimento & desenvolvimento , Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Reguladores de Crescimento de Plantas/metabolismo , Brotos de Planta/metabolismo , Brotos de Planta/crescimento & desenvolvimento , Plantas Geneticamente Modificadas
12.
Nat Biotechnol ; 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38267759

RESUMO

Clonal propagation of plants by induction of adventitious roots (ARs) from stem cuttings is a requisite step in breeding programs. A major barrier exists for propagating valuable plants that naturally have low capacity to form ARs. Due to the central role of auxin in organogenesis, indole-3-butyric acid is often used as part of commercial rooting mixtures, yet many recalcitrant plants do not form ARs in response to this treatment. Here we describe the synthesis and screening of a focused library of synthetic auxin conjugates in Eucalyptus grandis cuttings and identify 4-chlorophenoxyacetic acid-L-tryptophan-OMe as a competent enhancer of adventitious rooting in a number of recalcitrant woody plants, including apple and argan. Comprehensive metabolic and functional analyses reveal that this activity is engendered by prolonged auxin signaling due to initial fast uptake and slow release and clearance of the free auxin 4-chlorophenoxyacetic acid. This work highlights the utility of a slow-release strategy for bioactive compounds for more effective plant growth regulation.

13.
Bioconjug Chem ; 24(5): 766-71, 2013 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-23600997

RESUMO

We employed molecular modeling to design and then synthesize fluorescent ligands for the human progesterone receptor. Boron dipyrromethene (BODIPY) or tetramethylrhodamine were conjugated to the progesterone receptor antagonist RU486 (Mifepristone) through an extended hydrophilic linker. The fluorescent ligands demonstrated comparable bioactivity to the parent antagonist in live cells and triggered nuclear translocation of the receptor in a specific manner. The BODIPY labeled ligand was applied to investigate the dependency of progesterone receptor nuclear translocation on partner proteins and to show that functional heat shock protein 90 but not immunophilin FKBP52 activity is essential. A tissue distribution study indicated that the fluorescent ligand preferentially accumulates in tissues that express high levels of the receptor in vivo. The design and properties of the BODIPY-labeled RU486 make it a potential candidate for in vivo imaging of PR by positron emission tomography through incorporation of (18)F into the BODIPY core.


Assuntos
Compostos de Boro/análise , Corantes Fluorescentes/análise , Antagonistas de Hormônios/análise , Mifepristona/análise , Receptores de Progesterona/antagonistas & inibidores , Receptores de Progesterona/metabolismo , Compostos de Boro/metabolismo , Mama/citologia , Mama/metabolismo , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Corantes Fluorescentes/metabolismo , Antagonistas de Hormônios/metabolismo , Humanos , Mifepristona/metabolismo , Modelos Moleculares , Imagem Óptica , Receptores de Progesterona/análise
14.
Nat Plants ; 9(5): 785-802, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37024660

RESUMO

The plant hormone gibberellin (GA) regulates multiple developmental processes. It accumulates in the root elongating endodermis, but how it moves into this cell file and the significance of this accumulation are unclear. Here we identify three NITRATE TRANSPORTER1/PEPTIDE TRANSPORTER (NPF) transporters required for GA and abscisic acid (ABA) translocation. We demonstrate that NPF2.14 is a subcellular GA/ABA transporter, presumably the first to be identified in plants, facilitating GA and ABA accumulation in the root endodermis to regulate suberization. Further, NPF2.12 and NPF2.13, closely related proteins, are plasma membrane-localized GA and ABA importers that facilitate shoot-to-root GA12 translocation, regulating endodermal hormone accumulation. This work reveals that GA is required for root suberization and that GA and ABA can act non-antagonistically. We demonstrate how the clade of transporters mediates hormone flow with cell-file-specific vacuolar storage at the phloem unloading zone, and slow release of hormone to induce suberin formation in the maturation zone.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Ácido Abscísico/metabolismo , Giberelinas/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Arabidopsis/metabolismo , Transportadores de Nitrato , Hormônios/metabolismo , Regulação da Expressão Gênica de Plantas
15.
Nat Commun ; 13(1): 3614, 2022 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-35750661

RESUMO

Photoremovable protecting groups (PPGs) represent one of the main contemporary implementations of photochemistry in diverse fields of research and practical applications. For the past half century, organic and metal-complex PPGs were considered mutually exclusive classes, each of which provided unique sets of physical and chemical properties thanks to their distinctive structures. Here, we introduce the meso-methylporphyrin group as a prototype hybrid-class PPG that unites traditionally exclusive elements of organic and metal-complex PPGs within a single structure. We show that the porphyrin scaffold allows extensive modularity by functional separation of the metal-binding chromophore and up to four sites of leaving group release. The insertion of metal ions can be used to tune their spectroscopic, photochemical, and biological properties. We provide a detailed description of the photoreaction mechanism studied by steady-state and transient absorption spectroscopies and quantum-chemical calculations. Our approach applied herein could facilitate access to a hitherto untapped chemical space of potential PPG scaffolds.


Assuntos
Porfirinas , Íons , Luz , Metais , Fotoquímica
16.
Sci Adv ; 7(43): eabf6069, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34669479

RESUMO

The effects of abscisic acid (ABA) on plant growth, development, and response to the environment depend on local ABA concentrations. Here, we show that in Arabidopsis, ABA homeostasis is regulated by two previously unknown ABA transporters. Adenosine triphosphate­binding cassette subfamily G member 17 (ABCG17) and ABCG18 are localized to the plasma membranes of leaf mesophyll and cortex cells to redundantly promote ABA import, leading to conjugated inactive ABA sinks, thus restricting stomatal closure. ABCG17 and ABCG18 double knockdown revealed that the transporters encoded by these genes not only limit stomatal aperture size, conductance, and transpiration while increasing water use efficiency but also control ABA translocation from the shoot to the root to regulate lateral root emergence. Under abiotic stress conditions, ABCG17 and ABCG18 are transcriptionally repressed, promoting active ABA movement and response. The transport mechanism mediated by ABCG17 and ABCG18 allows plants to maintain ABA homeostasis under normal growth conditions.

17.
Bioconjug Chem ; 20(9): 1783-91, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19689155

RESUMO

The development and application of tools that allow labeling of proteins in vitro and in vivo is a highly active and interdisciplinary area of research. Self-immolative polymers (SIPs) are a unique type of molecules that respond to external stimuli by undergoing head-to-tail disassembly through a self-immolative fragmentation. We have demonstrated how these polymers can be applied as activity-linked labeling probes for proteins with catalytic activity. A real-time detection of the protein labeling can be monitored due to a change in the fluorescence emission wavelength of the probe during the polymer disassembly process. The SIP-based labeling approach showed considerable conservation of catalytic activity of the labeled protein and significant preference toward labeling of the activating protein.


Assuntos
Enzimas/química , Técnicas de Sonda Molecular , Polímeros/química , Enzimas/metabolismo , Corantes Fluorescentes , Sondas Moleculares , Polímeros/metabolismo
18.
Chem Sci ; 10(5): 1500-1505, 2019 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-30809367

RESUMO

Gibberellins (GAs) are ubiquitous plant hormones that coordinate central developmental and adaptive growth processes in plants. Accurate movement of GAs throughout the plant from their sources to their destination sites is emerging to be a highly regulated and directed process. We report on the development of novel photocaged gibberellins that, in combination with a genetically encoded GA-response marker, provide a unique platform to study GA movement at high-resolution, in real time and in living, intact plants. By applying this platform to the Arabidopsis thaliana endogenous bioactive gibberellin GA4, we measure kinetic parameters of its flow, such as decay length and velocity, in vivo.

19.
J Am Chem Soc ; 130(16): 5434-5, 2008 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-18376834

RESUMO

Smart polymers are special kinds of polymeric molecules that respond to external stimuli. We have developed a novel smart polymer designed to sequentially disassemble into its building blocks upon initiation by a triggering event at the polymer head. The polymer structure is based on a polyurethane backbone that disassembles through a domino-like, 1,6-elimination and decarboxylation reactions. We synthesized a self-immolative polymer that amplifies a single cleavage reaction into multiple release of fluorogenic molecules and confirmed the head-to-tail disassembly concept. These polymers can be used to prepare highly sensitive molecular sensors with large signal-to-noise ratios. The sensors should be useful for the detection of a wide range of biological and chemical activities through use of the appropriate trigger at the polymer head.


Assuntos
Dendrímeros/síntese química , Sistemas de Liberação de Medicamentos/métodos , Catálise , Descarboxilação , Isocianatos/química , Espectroscopia de Ressonância Magnética , Modelos Químicos , Poliuretanos/química
20.
Trends Plant Sci ; 23(5): 410-421, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29530380

RESUMO

Distribution patterns and finely-tuned concentration gradients of plant hormones govern plant growth and development. Gibberellin (GA) is a plant hormone regulating key processes in plants; many of them are of significant agricultural importance, such as seed germination, root and shoot elongation, flowering, and fruit patterning. Although studies have demonstrated that GA movement is essential for multiple developmental aspects, how GAs are transported throughout the plant and where exactly they accumulate remain largely unknown. Here, we summarize recent findings from studies of GA movement and localization, and discuss the importance of GA intermediates in long- and short-distance movement. We further review recently identified Arabidopsis GA transporters and highlight their complex specialization and robust functional redundancy in GA transport activity.


Assuntos
Regulação da Expressão Gênica de Plantas , Giberelinas/metabolismo , Plantas/genética , Plantas/metabolismo , Transporte Biológico , Regulação da Expressão Gênica no Desenvolvimento , Desenvolvimento Vegetal/genética , Transdução de Sinais/genética
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