title: New auxin analogs with growth-promoting effects in intact plants reveal a chemical strategy to improve hormone delivery.
abstract: Plant growth depends on the integration of environmental cues and phytohormone-signaling pathways. During seedling emergence, elongation of the embryonic stem (hypocotyl) serves as a readout for light and hormone-dependent responses. We screened 10,000 chemicals provided exogenously to light-grown seedlings and identified 100 compounds that promote hypocotyl elongation. Notably, one subset of these chemicals shares structural characteristics with the synthetic auxins, 2,4-dichlorophenoxyacetic acid (2,4-D), and 1-naphthaleneacetic acid (1-NAA); however, traditional auxins (e.g., indole-3-acetic acid [IAA], 2,4-D, 1-NAA) have no effect on hypocotyl elongation. We show that the new compounds act as "proauxins" akin to prodrugs. Our data suggest that these compounds diffuse efficiently to the hypocotyls, where they undergo cleavage at varying rates, releasing functional auxins. To investigate this principle, we applied a masking strategy and designed a pro-2,4-D. Unlike 2,4-D alone, this pro-2,4-D enhanced hypocotyl elongation. We further demonstrated the utility of the proauxins by characterizing auxin responses in light-grown hypocotyls of several auxin receptor mutants. These new compounds thus provide experimental access to a tissue previously inaccessible to exogenous application of auxins. Our studies exemplify the combined power of chemical genetics and biochemical analyses for discovering and refining prohormone analogs with selective activity in specific plant tissues. In addition to the utility of these compounds for addressing questions related to auxin and light-signaling interactions, one can envision using these simple principles to study other plant hormone and small molecule responses in temporally and spatially controlled ways.
authors.affiliation: Plant Biology Laboratory, The Salk Institute, La Jolla, CA 92037, USA.
authors.forename: Sigal
authors.initials: S
authors.lastname: Savaldi-Goldstein
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Baiga
authors.forename: Florence
authors.initials: F
authors.lastname: Pojer
authors.forename: Tsegeye
authors.initials: T
authors.lastname: Dabi
authors.forename: Cristina
authors.initials: C
authors.lastname: Butterfield
authors.forename: Geraint
authors.initials: G
authors.lastname: Parry
authors.forename: Aaron
authors.initials: A
authors.lastname: Santner
authors.forename: Nihal
authors.initials: N
authors.lastname: Dharmasiri
authors.forename: Yi
authors.initials: Y
authors.lastname: Tao
authors.forename: Mark
authors.initials: M
authors.lastname: Estelle
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Noel
authors.forename: Joanne
authors.initials: J
authors.lastname: Chory
mesh_terms: D017360:Arabidopsis / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000528:radiation effects; D002853:Chromatography, Liquid / Q000379:methods; D007210:Indoleacetic Acids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013058:Mass Spectrometry / Q000379:methods; D010937:Plant Growth Regulators / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010940:Plant Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D036226:Seedlings / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D013329:Structure-Activity Relationship
chemical_list: D007210:Indoleacetic Acids; D010937:Plant Growth Regulators; D010940:Plant Proteins; D011956:Receptors, Cell Surface; C046131:auxin receptor, plant