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Molecular locks and keys: the role of small molecules in phytohormone research.

Fonseca S, Rosado A, Vaughan-Hirsch J, Bishopp A, Chini A - Front Plant Sci (2014)

Bottom Line: How can we modulate hormone responses in one developmental context without inducing detrimental effects on other processes?The chemical genomics approaches rely on the identification of small molecules modulating different biological processes and have recently identified active forms of plant hormones and molecules regulating many aspects of hormone synthesis, transport and response.As we gain information about such compounds we can design small alterations to the chemical structure to further alter specificity, enhance affinity or modulate the activity of these compounds.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Genética Molecular de Plantas, Centro Nacional de Biotecnología- Consejo Superior de Investigaciones Científicas Madrid, Spain.

ABSTRACT
Plant adaptation, growth and development rely on the integration of many environmental and endogenous signals that collectively determine the overall plant phenotypic plasticity. Plant signaling molecules, also known as phytohormones, are fundamental to this process. These molecules act at low concentrations and regulate multiple aspects of plant fitness and development via complex signaling networks. By its nature, phytohormone research lies at the interface between chemistry and biology. Classically, the scientific community has always used synthetic phytohormones and analogs to study hormone functions and responses. However, recent advances in synthetic and combinational chemistry, have allowed a new field, plant chemical biology, to emerge and this has provided a powerful tool with which to study phytohormone function. Plant chemical biology is helping to address some of the most enduring questions in phytohormone research such as: Are there still undiscovered plant hormones? How can we identify novel signaling molecules? How can plants activate specific hormone responses in a tissue-specific manner? How can we modulate hormone responses in one developmental context without inducing detrimental effects on other processes? The chemical genomics approaches rely on the identification of small molecules modulating different biological processes and have recently identified active forms of plant hormones and molecules regulating many aspects of hormone synthesis, transport and response. We envision that the field of chemical genomics will continue to provide novel molecules able to elucidate specific aspects of hormone-mediated mechanisms. In addition, compounds blocking specific responses could uncover how complex biological responses are regulated. As we gain information about such compounds we can design small alterations to the chemical structure to further alter specificity, enhance affinity or modulate the activity of these compounds.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of the molecular targets of small molecules acting in different hormonal pathways. Concentric circles in the background represent the distinct biological processes in hormonal pathways: perception and signaling (gray inner circle), biosynthesis (yellow middle circle) and transport (white outer circle). Circles are divided in quadrants for distinct hormones, from the top clockwise: auxin, jasmonic acid (JA), gibberellins, strigolactones, cytokinins, brassinosteroids and abscisic acid (ABA). Ovals represent the molecular targets: receptor complexes (violet), signaling components (blue), biosynthetic enzyme (yellow) and catabolic enzymes (orange). Cylindrical shapes represent transporters and carriers. Molecules acting as activators are represented with an orange arrow toward their targets, whereas pink blocked arrows highlight antagonists and inhibitor molecules.
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Figure 1: Schematic representation of the molecular targets of small molecules acting in different hormonal pathways. Concentric circles in the background represent the distinct biological processes in hormonal pathways: perception and signaling (gray inner circle), biosynthesis (yellow middle circle) and transport (white outer circle). Circles are divided in quadrants for distinct hormones, from the top clockwise: auxin, jasmonic acid (JA), gibberellins, strigolactones, cytokinins, brassinosteroids and abscisic acid (ABA). Ovals represent the molecular targets: receptor complexes (violet), signaling components (blue), biosynthetic enzyme (yellow) and catabolic enzymes (orange). Cylindrical shapes represent transporters and carriers. Molecules acting as activators are represented with an orange arrow toward their targets, whereas pink blocked arrows highlight antagonists and inhibitor molecules.

Mentions: Fortunately, the development of genetic tools has gone hand in hand with advances in combinatorial synthesis. These advances have enabled access to highly diverse chemical libraries containing both wider spectra of molecular shapes and range of biological targets than traditional combinatorial libraries (Schreiber, 2000; Hicks and Raikhel, 2012). These chemical libraries are being used to overcome many of the limitations of purely genetic approaches. They can be used to address genetic redundancy, as small molecules are capable of modulating the active sites of whole classes of protein targets. They can also address gene lethality, as small molecules can enable the temporal and spatial blockage of specific hormonal responses in a reversible manner (McCourt and Desveaux, 2010; Tóth and van der Hoorn, 2010; Hicks and Raikhel, 2012). Hence, in the last two decades agrochemical biased libraries have been widely used in combined genetic and chemical screens aimed at the dissection of multiple physiological processes in plants. These screens have yielded valuable bioactive compounds such as gravacin (Rojas-Pierce et al., 2007), morlin (DeBolt et al., 2007), sortins (Zouhar et al., 2004; Rosado et al., 2011), hypostatin (Zhao et al., 2007), and endosidins (Robert et al., 2008; Drakakaki et al., 2011) (Figure 1 and Table 1). All these compounds are currently used to modify the activity of individual proteins or protein families in a tuneable, reversible and spatial-temporal controlled manner.


Molecular locks and keys: the role of small molecules in phytohormone research.

Fonseca S, Rosado A, Vaughan-Hirsch J, Bishopp A, Chini A - Front Plant Sci (2014)

Schematic representation of the molecular targets of small molecules acting in different hormonal pathways. Concentric circles in the background represent the distinct biological processes in hormonal pathways: perception and signaling (gray inner circle), biosynthesis (yellow middle circle) and transport (white outer circle). Circles are divided in quadrants for distinct hormones, from the top clockwise: auxin, jasmonic acid (JA), gibberellins, strigolactones, cytokinins, brassinosteroids and abscisic acid (ABA). Ovals represent the molecular targets: receptor complexes (violet), signaling components (blue), biosynthetic enzyme (yellow) and catabolic enzymes (orange). Cylindrical shapes represent transporters and carriers. Molecules acting as activators are represented with an orange arrow toward their targets, whereas pink blocked arrows highlight antagonists and inhibitor molecules.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4269113&req=5

Figure 1: Schematic representation of the molecular targets of small molecules acting in different hormonal pathways. Concentric circles in the background represent the distinct biological processes in hormonal pathways: perception and signaling (gray inner circle), biosynthesis (yellow middle circle) and transport (white outer circle). Circles are divided in quadrants for distinct hormones, from the top clockwise: auxin, jasmonic acid (JA), gibberellins, strigolactones, cytokinins, brassinosteroids and abscisic acid (ABA). Ovals represent the molecular targets: receptor complexes (violet), signaling components (blue), biosynthetic enzyme (yellow) and catabolic enzymes (orange). Cylindrical shapes represent transporters and carriers. Molecules acting as activators are represented with an orange arrow toward their targets, whereas pink blocked arrows highlight antagonists and inhibitor molecules.
Mentions: Fortunately, the development of genetic tools has gone hand in hand with advances in combinatorial synthesis. These advances have enabled access to highly diverse chemical libraries containing both wider spectra of molecular shapes and range of biological targets than traditional combinatorial libraries (Schreiber, 2000; Hicks and Raikhel, 2012). These chemical libraries are being used to overcome many of the limitations of purely genetic approaches. They can be used to address genetic redundancy, as small molecules are capable of modulating the active sites of whole classes of protein targets. They can also address gene lethality, as small molecules can enable the temporal and spatial blockage of specific hormonal responses in a reversible manner (McCourt and Desveaux, 2010; Tóth and van der Hoorn, 2010; Hicks and Raikhel, 2012). Hence, in the last two decades agrochemical biased libraries have been widely used in combined genetic and chemical screens aimed at the dissection of multiple physiological processes in plants. These screens have yielded valuable bioactive compounds such as gravacin (Rojas-Pierce et al., 2007), morlin (DeBolt et al., 2007), sortins (Zouhar et al., 2004; Rosado et al., 2011), hypostatin (Zhao et al., 2007), and endosidins (Robert et al., 2008; Drakakaki et al., 2011) (Figure 1 and Table 1). All these compounds are currently used to modify the activity of individual proteins or protein families in a tuneable, reversible and spatial-temporal controlled manner.

Bottom Line: How can we modulate hormone responses in one developmental context without inducing detrimental effects on other processes?The chemical genomics approaches rely on the identification of small molecules modulating different biological processes and have recently identified active forms of plant hormones and molecules regulating many aspects of hormone synthesis, transport and response.As we gain information about such compounds we can design small alterations to the chemical structure to further alter specificity, enhance affinity or modulate the activity of these compounds.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Genética Molecular de Plantas, Centro Nacional de Biotecnología- Consejo Superior de Investigaciones Científicas Madrid, Spain.

ABSTRACT
Plant adaptation, growth and development rely on the integration of many environmental and endogenous signals that collectively determine the overall plant phenotypic plasticity. Plant signaling molecules, also known as phytohormones, are fundamental to this process. These molecules act at low concentrations and regulate multiple aspects of plant fitness and development via complex signaling networks. By its nature, phytohormone research lies at the interface between chemistry and biology. Classically, the scientific community has always used synthetic phytohormones and analogs to study hormone functions and responses. However, recent advances in synthetic and combinational chemistry, have allowed a new field, plant chemical biology, to emerge and this has provided a powerful tool with which to study phytohormone function. Plant chemical biology is helping to address some of the most enduring questions in phytohormone research such as: Are there still undiscovered plant hormones? How can we identify novel signaling molecules? How can plants activate specific hormone responses in a tissue-specific manner? How can we modulate hormone responses in one developmental context without inducing detrimental effects on other processes? The chemical genomics approaches rely on the identification of small molecules modulating different biological processes and have recently identified active forms of plant hormones and molecules regulating many aspects of hormone synthesis, transport and response. We envision that the field of chemical genomics will continue to provide novel molecules able to elucidate specific aspects of hormone-mediated mechanisms. In addition, compounds blocking specific responses could uncover how complex biological responses are regulated. As we gain information about such compounds we can design small alterations to the chemical structure to further alter specificity, enhance affinity or modulate the activity of these compounds.

No MeSH data available.


Related in: MedlinePlus