A Cyclotide Isolated from Noisettia orchidiflora (Violaceae)^[*]

Abstract

Biologically active cyclotides have been found on some flowering plants species and are involved in the role of the plant protection. As part of studies focusing on peptides from Brazilian plant species, we are reporting the detection by LC-MS of several cyclotides from leaves and stems of Noisettia orchidiflora (Violaceae). From stems it was possible to isolate and characterize a cyclotide named Nor A. Its primary structure (amino acid sequence) was established by MALDI-TOF-MS, based on the y- and b-type ion series, after reduction and alkylation reactions, as well as enzymatic digestion using the enzymes endoproteinase glutamic acid (endoGlu-C), trypsin, and chymotrypsin. Furthermore, the amino acid analysis was also described.

Key words

cyclotide - Noisettia orchidiflora - Violaceae - cyclic peptide - MALDI TOF/TOF - Nor A

^* Dedicated to Professor Dr. Robert Verpoorte in recognition of his outstanding contribution to natural products research.

^** These authors contributed equally to this work.

• References

• 1 Craik DJ, Daly NL, Bond T, Waine C. Plant cyclotides: a unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif. J Mol Biol 1999; 294: 1327-1336
• 2 Craik DJ, Daly NL, Waine C. The cystine knot motif in toxins and implications for drug design. Toxicon 2001; 39: 43-60
• 3 Colgrave ML, Craik DJ. Thermal, chemical, and enzymatic stability of the cyclotide kalata B1: the importance of the cyclic cystine knot. Biochemistry 2004; 43: 5965-5975
• 4 Göransson U, Malik S, Slazak B. Cyclotides in the Violaceae. Adv Bot Res 2015; 76: 15-49
• 5 Barbeta BL, Marshall AT, Gillon AD, Craik DJ, Anderson MA. Plant cyclotides disrupt epithelial cells in the midgut of lepidopteran larvae. Proc Natl Acad Sci U S A 2008; 105: 1221-1225
• 6 Colgrave ML, Kotze AC, Huang YH, OʼGrady J, Simonsen SM, Craik DJ. Cyclotides: natural, circular plant peptides that possess significant activity against gastrointestinal nematode parasites of sheep. Biochemistry 2008; 47: 5581-5589
• 7 Plan MRR, Saska I, Cagauan AG, Craik DJ. Backbone cyclised peptides from plants show molluscicidal activity against the rice pest Pomacea canaliculata (golden apple snail). J Agric Food Chem 2008; 56: 5237-5241
• 8 Göransson U, Sjögren M, Svangård E, Claeson P, Bohlin L. Reversible antifouling effect of the cyclotide cycloviolacion O2 against barnacles. J Nat Prod 2004; 67: 1287-1290
• 9 Gruber CW, Čemažar M, Anderson MA, Craik DJ. Insecticidal plant cyclotides and related cysteine knot toxins. Toxicon 2007; 49: 561-575
• 10 Pinto MFS, Fensterseifer ICM, Migliolo L, Sousa DA, Capdville G, Arboleda-Valencia JW, Colgrave ML, Craik DJ, Magalhães BS, Dias SC, Franco OL. Identification and structural characterization of novel cyclotide with activity against an insect pest of sugar cane. J Biol Chem 2012; 287: 134-147
• 11 Saether O, Craik DJ, Campbell ID, Sletten K, Juul J, Norman DG. Elucidation of the primary and three-dimensional structure of the uterotonic polypeptide kalata B1. Biochemistry 1995; 34: 4147-4158
• 12 Gran L, Sletten K, Skjedal L. Cyclic peptides from Oldenlandia affinis DC. Molecular and biological properties. Chem Biodivers 2008; 5: 2014-2022
• 13 Pränting M, Loov C, Burman R, Göransson U, Andersson DI. The cyclotide cycloviolacin O2 from Viola odorata has potent bactericidal activity against Gram-negative bacteria. J Antimicrob Chemother 2010; 65: 1964-1971
• 14 Ovesen RG, Brandt KK, Göransson U, Nielsen J, Hansen HC, Cedergreen N. Biomedicine in the environment: cyclotides constitute potent natural toxins in plants and soil bacteria. Environ Toxicol Chem 2011; 30: 1190-1196
• 15 Gustafson KR, Mckee TC, Bokesch HR. Anti-HIV cyclotides. Curr Protein Pept Sc 2004; 5: 331-340
• 16 Wang CK, Colgrave ML, Gustafson KR, Ireland DC, Göransson U, Craik DJ. Anti-HIV cyclotides from the Chinese medicinal herb Viola yedoensis . J Nat Prod 2008; 71: 47-52
• 17 Ding X, Bai D, Qian J. Novel cyclotides from Hedyotis biflora inhibit proliferation and migration of pancreatic cancer cell in vitro and in vivo . Med Chem Res 2014; 23: 1406-1413
• 18 He W, Chan LY, Zeng G, Daly NL, Craik DJ, Tan N. Isolation and characterization of cytotoxic cyclotides from Viola philippica . Peptides 2011; 32: 1719-1723
• 19 Hellinger R, Koehbach J, Puigpinós A, Clark RJ, Tarragó T, Giralt E, Gruber CW. Inhibition of human prolyl oligopeptidase activity by the cyclotide psyol 2 isolated from Psychotria solitudinum . J Nat Prod 2015; 78: 1073-1082
• 20 Gründemann C, Koehbach J, Huber R, Gruber CW. Do plant cyclotides have potential as immunosuppressant peptides?. J Nat Prod 2012; 75: 167-174
• 21 Gründemann C, Thell K, Lengen K, Garcia-Käufer M, Huang YH, Huber R, Craik DJ, Schabbauer G, Gruber CW. Cyclotides suppress human T-lymphocyte proliferation by an interleukin 2-dependent mechanism. PLoS One 2013; 8: e68016
• 22 Thell K, Hellinger R, Sahin E, Michenthaler P, Gold-Binder M, Haider T, Kuttke M, Liutkevičiūtė Z, Göransson U, Gründemann C, Schabbauer G, Gruber CW. Oral activity of a nature-derived cyclic peptide for the treatment of multiple sclerosis. Proc Natl Acad Sci U S A 2016; 113: 3960-3965
• 23 Koehbach J, Attah AF, Berger A, Hellinger R, Kutchan TM, Carpenter EJ, Rolf M, Sonibare MA, Moody JO, Wong GKS, Dessein S, Greger H, Gruber CW. Cyclotide discovery in Gentianales revisited – identification and characterization of cyclic cystine-knot peptides and their phylogenetic distribution in Rubiaceae plants. Proc Natl Acad Sci U S A 2013; 100: 438-451
• 24 Fahradpour M, Keov P, Tognola C, Perez-Santamarina E, McCormick PJ, Ghassempour A, Gruber CW. Cyclotides isolated from an ipecac root extract antagonize the corticotropin releasing factor type 1 receptor. Front Pharmacol 2017; 8: 616
• 25 Hernandez JF, Gagnon J, Chiche L, Nguyen TM, Andrieu JP, Heitz A, Hong TT, Pham TT, Nguyen DL. Squash trypsin inhibitors from Momordica cochinchinensis exhibit an atypical macrocyclic structure. Biochemistry 2000; 39: 5722-5730
• 26 Poth AG, Mylne JS, Grassl J, Lyons RE, Millar AH, Colgrave ML, Craik DJ. Cyclotides associate with leaf vasculature and are the products of a novel precursor in Petunia (Solanaceae). J Biol Chem 2012; 287: 27033-27046
• 27 Poth AG, Colgrave ML, Philip R, Kerenga B, Daly NL, Anderson MA, Craik DJ. Discovery of cyclotides in the Fabaceae plant family provides new insights into the cyclization, evolution, and distribution of circular proteins. ACS Chem Biol 2011; 6: 345-355
• 28 Nguyen GK, Zhang S, Nguyen NT, Nguyen PQ, Chiu MS, Hardjojo A. Discovery and characterization of novel cyclotides originated from chimeric precursors consisting of albumin-1 chain a and cyclotide domains in the Fabaceae family. J Biol Chem 2011; 286: 24275-24287
• 29 Burman R, Yeshak MY, Larsson S, Craik DJ, Rosengren KJ, Göransson U. Distribution of circular proteins in plants: large-scale mapping of cyclotides in the Violaceae. Front Plant Sci 2015; 6: 855
• 30 The Plant List. Available at: http://www.theplantlist.org/tpl1.1/record/tro-33800548 Accessed April 16, 2018
• 31 Daly DC, Silveira M, Ferreira EL. Floristics and economic botany of Acre, Brazil. Available at: https://www.nybg.org/bsci/acre/www2/vname_t.html Accessed January 16, 2018
• 32 DeFilipps RA, Maina SL, Crepin J. Medicinal plants of the Guianas (Guyana, Surinam, French Guiana). Available at: http://botany.si.edu/bdg/medicinal/Medicinal_plants_master.pdf Accessed January 16, 2018
• 33 Trabi M, Svangård E, Herrmann A, Göransson U, Claeson P, Craik DJ, Bohlin L. Variations in cyclotide expression in Viola species. J Nat Prod 2004; 67: 806-810
• 34 Ireland DC, Clark RJ, Daly NL, Craik DJ. Isolation, sequencing, and structure-activity relationships of cyclotides. J Nat Prod 2010; 73: 1610-1622
• 35 Broussalis AM, Göransson U, Coussio JD, Ferraro G, Martino V, Claeson P. First cyclotide from Hybanthus (Violaceae). Phytochemistry 2001; 58: 47-51
• 36 Gustafson KR, Sowder II RC, Henderson LE, Parsons IC, Kashman Y, Cardellina II JH, McMahon JB, Buckheit RW, Pannell LK, Boyd MR. Circulins A and B: novel HIV-inhibitory macrocyclic peptides from the tropical tree Chassalia parvifolia . J Am Chem Soc 1994; 116: 9337-9338
• 37 Wang CK, Craik DJ. Cybase, the database of cyclic proteins sequences and structures, with applications in protein discovery and engineering. Available at: http://www.cybase.org.au Accessed January 15, 2018
• 38 Hellinger R, Koehbach J, Soltis DE, Carpenter EJ, Wong GKS, Gruber CW. Peptidomics of circular cysteine-rich plant peptides: analysis of the diversity of cyclotides from Viola tricolor by transcriptome and proteome mining. J Proteome Res 2015; 14: 4851-4862
• 39 Ravipati AS, Poth AG, Henriques ST, Bhandari M, Huang YH, Nino J, Colgrave ML, Craik DJ. Understanding the diversity and distribution of cyclotides from plants of varied genetic origin. J Nat Prod 2017; 80: 1522-1530
• 40 Gruber CW, Elliott AG, Ireland DC, Delprete PG, Dessein S, Göransson U, Trabi M, Wang CK, Kinghorn AB, Robbrecht E, Craik DJ. Distribution and evolution of circular miniproteins in flowering plants. Plant Cell 2008; 20: 2471-2483
• 41 Pinto MEF, Batista JM, Koehbach J, Gaur P, Sharma A, Nakabashi M, Cilli EM, Giesel GM, Verli H, Gruber CW, Blanch EW, Tavares JF, Silva MS, Garcia CRS, Bolzani VS. Ribifolin, an orbitide from Jatropha ribifolia, and its potential antimalarial activity. J Nat Prod 2015; 78: 374-380
• 42 NCBI Resource Coordinators. Database resources of the National Center for Biotechnology Information. Nucleic Acids Res 2018; 46: D8-D13