Skip to main content
SpringerLink
Log in

Vectorization of agrochemicals: amino acid carriers are more efficient than sugar carriers to translocate phenylpyrrole conjugates in the Ricinus system

  • Environmental and human health issues related to pesticides: from usage and environmental fate to impact
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

Producing quality food in sufficient quantity while using less agrochemical inputs will be one of the great challenges of the twenty-first century. One way of achieving this goal is to greatly reduce the doses of plant protection compounds by improving the targeting of pests to eradicate. Therefore, we developed a vectorization strategy to confer phloem mobility to fenpiclonil, a contact fungicide from the phenylpyrrole family used as a model molecule. It consists in coupling the antifungal compound to an amino acid or a sugar, so that the resulting conjugates are handled by active nutrient transport systems. The method of click chemistry was used to synthesize three conjugates combining fenpiclonil to glucose or glutamic acid with a spacer containing a triazole ring. Systemicity tests with the Ricinus model have shown that the amino acid promoiety was clearly more favorable to phloem mobility than that of glucose. In addition, the transport of the amino acid conjugate is carrier mediated since the derivative of the L series was about five times more concentrated in the phloem sap than its counterpart of the D series. The systemicity of the L-derivative is pH dependent and almost completely inhibited by the protonophore carbonyl cyanide 3-chlorophenylhydrazone (CCCP). These data suggest that the phloem transport of the L-derivative is governed by a stereospecific amino acid carrier system energized by the proton motive force.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Albert A (1958) Chemical aspects of selective toxicity. Nature 182:421–422

    Article  CAS  Google Scholar 

  • Avram S, Funar-Timofei S, Borota A, Chennamaneni SR, Manchala AK, Muresan S (2014) Quantitative estimation of pesticide-likeness for agrochemical discovery. J Cheminform 6:11. doi:10.1186/s13321-014-0042-6

    Article  CAS  Google Scholar 

  • Barlow CA, Randolph PA (1978) Quality and quantity of plant sap available to pea aphid (Acyrthosiphon pisum Harris aphididae). Ann Entomol Soc Am 71:46–48

    Article  CAS  Google Scholar 

  • Bonnemain JL (2010) Aphids as biological models and agricultural pests. C. R. Biol. 333:461–463. doi:10.1016/j.crvi.2010.04.002

    Article  Google Scholar 

  • Bouché-Pillon S, Fleurat-Lessard P, Fromont JC, Serrano R, Bonnemain JL (1994a) Immunolocalization of the plasma membrane H+-ATPase in minor veins of Vicia faba in relation to phloem loading. Plant Physiol 105:691–697

    Article  Google Scholar 

  • Bouché-Pillon S, Fleurat-Lessard P, Serrano R, Bonnemain JL (1994b) Asymmetric distribution of the plasma membrane H+-ATPase in embryos of Vicia faba L with special reference to transfer cells. Planta 193:392–397

    Article  Google Scholar 

  • Cagnoni AJ, Varela O, Gouin SG, Kovensky J, Uhrig ML (2011) Synthesis of multivalent glycoclusters from 1-thio-beta-D-galactose and their inhibitory activity against the beta-galactosidase from E. coli. J. Org. Chem. 76:3064–3077. doi:10.1021/jo102421e

    Article  CAS  Google Scholar 

  • Chollet J-F, Couderchet M, Bonnemain J-L (2014) Crop protection: new strategies for sustainable development. Environ Sci Pollut Res Int 21:4793–4796. doi:10.1007/s11356-014-2567-7

    Article  Google Scholar 

  • Chollet JF, Delétage C, Faucher M, Miginiac L, Bonnemain JL (1997) Synthesis and structure-activity relationships of some pesticides with an alpha-amino acid function. Biochim Biophys Acta 1336:331–341. doi:10.1016/s0304-4165(97)00041-x

    Article  CAS  Google Scholar 

  • Chollet JF, Rocher F, Jousse C, Deletage-Grandon C, Bashiardes G, Bonnemain JL (2004) Synthesis and phloem mobility of acidic derivatives of the fungicide fenpiclonil. Pest Manag Sci 60:1063–1072. doi:10.1002/ps.906

    Article  CAS  Google Scholar 

  • Chollet JF, Rocher F, Jousse C, Deletage-Grandon C, Bashiardes G, Bonnemain JL (2005) Acidic derivatives of the fungicide fenpiclonil: effect of adding a methyl group to the N-substituted chain on systemicity and fungicidal activity. Pest Manag Sci 61:377–382. doi:10.1002/ps.977

    Article  CAS  Google Scholar 

  • Dedryver CA, Le Ralec A, Fabre F (2010) The conflicting relationships between aphids and men: a review of aphid damage and control strategies. C. R. Biol. 333:539–553. doi:10.1016/j.crvi.2010.03.009

    Article  Google Scholar 

  • DeGorter MK, Xia CQ, Yang JJ, Kim RB (2012) Drug transporters in drug efficacy and toxicity. Annu Rev Pharmacol Toxicol 52:249–273. doi:10.1146/annurev-pharmtox-010611-134529

    Article  CAS  Google Scholar 

  • Delétage-Grandon C, Chollet JF, Faucher M, Rocher F, Komor E, Bonnemain JL (2001) Carrier-mediated uptake and phloem systemy of a 350-Dalton chlorinated xenobiotic with an alpha-amino acid function. Plant Physiol 125:1620–1632. doi:10.1104/pp.125.4.1620

    Article  Google Scholar 

  • Despeghel JP, Delrot S (1983) Energetics of amino acid uptake by Vicia faba leaf tissues. Plant Physiol 71:1–6. doi:10.1104/pp.71.1.1

    Article  CAS  Google Scholar 

  • DeWitt ND, Sussman MR (1995) Immunocytological localization of an epitope-tagged plasma membrane proton pump (H+-ATPase) in phloem companion cells. Plant Cell 7:2053–2067

    CAS  Google Scholar 

  • Dinant S, Bonnemain JL, Girousse C, Kehr J (2010) Phloem sap intricacy and interplay with aphid feeding. C. R. Biol. 333:504–515. doi:10.1016/j.crvi.2010.03.008

    Article  Google Scholar 

  • Dogimont C, Bendahmane A, Chovelon V, Boissot N (2010) Host plant resistance to aphids in cultivated crops: genetic and molecular bases, and interactions with aphid populations. C R Biol 333:566–573. doi:10.1016/j.crvi.2010.04.003

    Article  CAS  Google Scholar 

  • Dufaud A, Chollet JF, Rudelle J, Miginiac L, Bonnemain JL (1994) Derivatives of pesticides with an alpha-amino acid function—synthesis and effect on threonine uptake. Pestic Sci 41:297–304. doi:10.1002/ps.2780410403

    Article  CAS  Google Scholar 

  • Edgington LV (1981) Structural requirements of systemic fungicides. Annu Rev Phytopathol 19:107–124. doi:10.1146/annurev.py.19.090181.000543

    Article  CAS  Google Scholar 

  • Fan W, Wu Y, Li XK, Yao N, Li X, Yu YG, Hai L (2011) Design, synthesis and biological evaluation of brain-specific glucosyl thiamine disulfide prodrugs of naproxen. Eur J Med Chem 46:3651–3661. doi:10.1016/j.ejmech.2011.05.029

    Article  CAS  Google Scholar 

  • Frommer WB, Kwart M, Hirner B, Fischer WN, Hummel S, Ninnemann O (1994) Transporters for nitrogenous compounds in plants. Plant Mol Biol 26:1651–1670. doi:10.1007/bf00016495

    Article  CAS  Google Scholar 

  • Giacomini KM et al (2010) Membrane transporters in drug development. Nat Rev Drug Discov 9:215–236. doi:10.1038/nrd3028

    Article  CAS  Google Scholar 

  • Girousse C, Bonnemain JL, Delrot S, Bournoville R (1991) Sugar and amino acid composition of phloem sap of Medicago sativa—a comparative study of 2 collecting methods. Plant Physiol Biochem 29:41–48

    CAS  Google Scholar 

  • Gynther M, Laine K, Ropponen J, Leppanen J, Mannila A, Nevalainen T, Savolainen J, Jarvinen TT, Rautio J (2008) Large neutral amino acid transporter enables brain drug delivery via prodrugs. J Med Chem 51:932–936. doi:10.1021/jm701175d

    Article  CAS  Google Scholar 

  • Hayashi H, Chino M (1986) Collection of pure phloem sap from wheat and its chemical composition. Plant Cell Physiol 27:1387–1393

    Article  CAS  Google Scholar 

  • Hu AL, Yang W, Xu HH (2010) Novel fluorescent conjugate containing glucose and NBD and its carrier-mediated uptake by tobacco cells. J Photochem Photobiol B 101:215–223. doi:10.1016/j.jphotobiol.2010.07.006

    Article  CAS  Google Scholar 

  • Huisgen R, Knorr R, Mobius L, Szeimies G (1965) 1.3-Dipolare cycloadditionen. 23. Einige beobachtungen zur addition organischer azide an cc-dreifachbindungen. Chem Ber Recl 98:4014–4021. doi:10.1002/cber.19650981228

    Article  CAS  Google Scholar 

  • Husted S, Schjoerring JK (1995) Apoplastic pH and ammonium concentration in leaves of Brassica napus L. Plant Physiol 109:1453–1460

    Article  CAS  Google Scholar 

  • Kallarackal J, Komor E (1989) Transport of hexoses by the phloem of Ricinus communis L seedlings. Planta 177:336–341. doi:10.1007/bf00403591

    Article  CAS  Google Scholar 

  • Kolb HC, Finn MG, Sharpless KB (2001) Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int Ed 40:2004–2021. doi:10.1002/1521-3773(20010601)40:11<2004::aid-anie2004>3.0.co;2-5

    Article  CAS  Google Scholar 

  • Komor E, Rotter M, Waldhauser J, Martin E, Cho BH (1980) Sucrose proton symport for phloem loading in the Ricinus seedling. Ber Dtsch bot Ges 93:211–219

    CAS  Google Scholar 

  • Li ZC, Bush DR (1992) Structural determinants in substrate recognition by proton amino acid symports in plasma membrane vesicles isolated from sugar beet leaves. Arch Biochem Biophys 294:519–526. doi:10.1016/0003-9861(92)90719-d

    Article  CAS  Google Scholar 

  • Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (2012) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Del Rev 64:4–17. doi:10.1016/j.addr.2012.09.019

    Article  Google Scholar 

  • Liu DD, Chao WM, Turgeon R (2012) Transport of sucrose, not hexose, in the phloem. J Exp Bot 63:4315–4320. doi:10.1093/jxb/ers127

    Article  CAS  Google Scholar 

  • López-Millán AF, Morales F, Abadia A, Abadia J (2000) Effects of iron deficiency on the composition of the leaf apoplastic fluid and xylem sap in sugar beet. Implications for iron and carbon transport. Plant Physiol 124:873–884. doi:10.1104/pp.124.2.873

    Article  Google Scholar 

  • Loubet B, Milford C, Hill PW, Tang YS, Cellier P, Sutton MA (2002) Seasonal variability of apoplastic NH4+ and pH in an intensively managed grassland. Plant Soil 238:97–110. doi:10.1023/a:1014208926195

    Article  CAS  Google Scholar 

  • Mannhold R, Kubinyi H, Folkers G, van de Waterbeemd H, Testa B (eds) (2009) Drug bioavailability: estimation of solubility, permeability, absorption and bioavailability, 40. Wiley, Weinheim

    Google Scholar 

  • Mayer T, Maier ME (2007) Design and synthesis of a tag-free chemical probe for photoaffinity labeling. Eur. J. Org. Chem.: 4711–4720 doi: 10.1002/ejoc.200700188

  • Morsomme P, Boutry M (2000) The plant plasma membrane H+-ATPase: structure, function and regulation. Biochim Biophys Acta 1465:1–16. doi:10.1016/s0005-2736(00)00128-0

    Article  CAS  Google Scholar 

  • Mühling KH, Plieth C, Hansen UP, Sattelmacher B (1995) Apoplastic pH of intact leaves of Vicia faba as influenced by light. J Exp Bot 46:377–382. doi:10.1093/jxb/46.4.377

    Article  Google Scholar 

  • Mühling KH, Läuchli A (2000) Light-induced pH and K+ changes in the apoplast of intact leaves. Planta 212:9–15. doi:10.1007/s004250000374

    Article  Google Scholar 

  • Nyfeler R, Ackermann P (1992) Phenylpyrroles, a new class of agricultural fungicides related to the natural antibiotic pyrrolnitrin. ACS Symp Ser 504:395–404

    Article  CAS  Google Scholar 

  • Pfanz H, Dietz KJ (1987) A fluorescence method for the determination of the apoplastic proton concentration in intact leaf tissues. J Plant Physiol 129:41–48

    Article  CAS  Google Scholar 

  • Pitann B, Schubert S, Muhling KH (2009) Decline in leaf growth under salt stress is due to an inhibition of H+-pumping activity and increase in apoplastic pH of maize leaves. J Plant Nutr Soil Sci 172:535–543. doi:10.1002/jpln.200800349

    Article  CAS  Google Scholar 

  • Rocher F, Chollet JF, Jousse C, Bonnemain JL (2006) Salicylic acid, an ambimobile molecule exhibiting a high ability to accumulate in the phloem. Plant Physiol 141:1684–1693. doi:10.1104/pp.106.082537

    Article  CAS  Google Scholar 

  • Rocher F, Chollet JF, Legros S, Jousse C, Lemoine R, Faucher M, Bush DR, Bonnemain JL (2009) Salicylic acid transport in Ricinus communis involves a pH-dependent carrier system in addition to diffusion. Plant Physiol 150:2081–2091. doi:10.1104/pp.109.140095

    Article  CAS  Google Scholar 

  • Rocher F, Roblin G, Chollet J-F (2016) Modifications of the chemical structure of phenolics differentially affect physiological activities in pulvinar cells of Mimosa pudica L. II. Influence of various molecular properties in relation to membrane transport. Environ. Sci. Pollut. Res. Int.: In press doi: 10.1007/s11356-016-6048-z

  • Rostovtsev VV, Green LG, Fokin VV, Sharpless KB (2002) A stepwise Huisgen cycloaddition process: copper(I)-catalyzed regioselective “ligation” of azides and terminal alkynes. Angew Chem Int Ed 41:2596–2599. doi:10.1002/1521-3773(20020715)41:14<2596::aid-anie2596>3.0.co;2-4

    Article  CAS  Google Scholar 

  • Sheehan JC, Hess GP (1955) A new method of forming peptide bonds. J Am Chem Soc 77:1067–1068. doi:10.1021/ja01609a099

    Article  CAS  Google Scholar 

  • Sheehan JC, Boshart GL, Cruickshank PA (1961) Convenient synthesis of water-soluble carbodiimides. J. Org. Chem. 26:2525–2528. doi:10.1021/jo01351a600

    Article  CAS  Google Scholar 

  • Siebum AHG, Tsang RKF, van der Steen R, Raap J, Lugtenburg J (2004) Synthesis of (epsilon-C-13-,epsilon N-15)-enriched L-lysine—establishing schemes for the preparation of all possible C-13 and N-15 isotopomers of L-lysine, L-ornithine, and L-proline. Eur. J. Org. Chem.: 4391–4396 doi: 10.1002/ejoc.200400370

  • Stella VJ, Borchardt RT, Hageman MJ, Oliyai R, Maag H, Tilley JW (Editors), 2007: Prodrugs challenges and rewards. Part 1. Springer-Verlag, New York, XVIII, 1464 pp

  • Sugano K, Kansy M, Artursson P, Avdeef A, Bendels S, Di L, Ecker GF, Faller B, Fischer H, Gerebtzoff G, Lennernaes H, Senner F (2010) Coexistence of passive and carrier-mediated processes in drug transport. Nat Rev Drug Discov 9:597–614. doi:10.1038/nrd3187

    Article  CAS  Google Scholar 

  • Tice CM (2001) Selecting the right compounds for screening: does Lipinski’s rule of 5 for pharmaceuticals apply to agrochemicals? Pest Manage Sci 57:3–16. doi:10.1002/1526-4998(200101)57:1<3::aid-ps269>3.0.co;2-6

    Article  CAS  Google Scholar 

  • Tornoe CW, Christensen C, Meldal M (2002) Peptidotriazoles on solid phase: 1,2,3-triazoles by regiospecific copper(I)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. J Org Chem 67:3057–3064. doi:10.1021/jo011148j

    Article  CAS  Google Scholar 

  • Usuki T, Sugimura T, Komatsu A, Koseki Y (2014) Biomimetic chichibabin pyridine synthesis of the COPD biomarkers and elastin cross-linkers isodesmosine and desmosine. Org Lett 16:1672–1675. doi:10.1021/ol500333t

    Article  CAS  Google Scholar 

  • van Pee KH, Ligon JM (2000) Biosynthesis of pyrrolnitrin and other phenylpyrrole derivatives by bacteria. Nat Prod Rep 17:157–164. doi:10.1039/a902138h

    Article  Google Scholar 

  • Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD (2002) Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem 45:2615–2623. doi:10.1021/jm020017n

    Article  CAS  Google Scholar 

  • Wang CJ, Liu ZQ (2007) Foliar uptake of pesticides—present status and future challenge. Pestic Biochem Physiol 87:1–8. doi:10.1016/j.pestbp.2006.04.004

    Article  CAS  Google Scholar 

  • Wu HX, Yang W, Zhang ZX, Huang T, Yao GK, Xu HH (2012) Uptake and phloem transport of glucose-fipronil conjugate in Ricinus communis involve a carrier-mediated mechanism. J Agric Food Chem 60:6088–6094. doi:10.1021/jf300546t

    Article  CAS  Google Scholar 

  • Yang W, Wu HX, Xu HH, Hu AL, Lu ML (2011) Synthesis of glucose-fipronil conjugate and its phloem mobility. J Agric Food Chem 59:12534–12542. doi:10.1021/jf2031154

    Article  CAS  Google Scholar 

  • Zawilska JB, Wojcieszak J, Olejniczak AB (2013) Prodrugs: a challenge for the drug development. Pharmacol Rep 65:1–14

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors are grateful to FranceAgriMer, InterLoire, and Jas Hennessy & Co. for their financial support of this work. This work was also supported by China Scholarship Council (Hanxiang Wu grant for his PhD). We would like to thank Emilie Dugaro for his kind collaboration in organic synthesis and Christine Bonnemain and Dr. Rémi Lemoine for their help to improve the manuscript.

Author information

Authors and Affiliations

  1. Institut de Chimie des Milieux et des Matériaux de Poitiers (IC2MP), Unité Mixte de Recherche CNRS 7285, Université de Poitiers, 4 rue Michel Brunet, TSA 51106, 86073, Poitiers Cedex 9, France

    Hanxiang Wu, Sophie Marhadour, Cécile Marivingt-Mounir & Jean-François Chollet

  2. Laboratoire Écologie et Biologie des Interactions, Unité Mixte de Recherche CNRS 7267, Université de Poitiers, 3 rue Jacques Fort, TSA 51106, 86073, Poitiers Cedex 9, France

    Hanxiang Wu & Jean-Louis Bonnemain

  3. Guizhou Tea Reasearch Institute, Guizhou Academy of Agricultural Science, Guiyang, Guizhou, 550009, China

    Zhi-Wei Lei & Wen Yang

Authors
  1. Hanxiang Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sophie Marhadour
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhi-Wei Lei
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wen Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cécile Marivingt-Mounir
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jean-Louis Bonnemain
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jean-François Chollet
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jean-François Chollet.

Additional information

Responsible editor: Philippe Garrigues

Hanxiang Wu and Sophie Marhadour contributed equally to the paper.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, H., Marhadour, S., Lei, ZW. et al. Vectorization of agrochemicals: amino acid carriers are more efficient than sugar carriers to translocate phenylpyrrole conjugates in the Ricinus system. Environ Sci Pollut Res 25, 14336–14349 (2018). https://doi.org/10.1007/s11356-016-8107-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-016-8107-x

Keywords

Search

Navigation