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Ronald Maul - One of the best experts on this subject based on the ideXlab platform.
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ImpAct of experimentAl thermAl processing of ArtificiAlly contAminAted peA products on ochrAtoxin A And Phomopsin A
Mycotoxin Research, 2020Co-Authors: Birgitta Maria Kunz, Sascha Rohn, Alexander Voß, Julia Dalichow, Stefan Weigel, Ronald MaulAbstract:Fungi of Aspergillus And Penicillium genus cAn infect peAs ( Pisum sAtivum ), leAding to A contAminAtion with the nephrotoxic And cArcinogenic ochrAtoxin A (OTA). Under unfAvourAble conditions, A fungus primArily found on lupines, DiApothe toxicA , mAy Also grow on peAs And produce the hepAtotoxic Phomopsin A (PHOA). To study the effect of processing on OTA And PHOA content, two model products—wheAt/rye-mixed breAd with peA flour Addition And peA pAstA—were mAnufActured At smAll-business scAle from ArtificiAlly contAminAted peA flour. The decreAse of OTA And PHOA contents were monitored Along the production process As indicAtors for toxin trAnsformAtion. PeA breAd dough wAs subjected to proofing for 30–40 min At 32 °C And bAked At 250 °C to 230 °C for 40 min. OTA content (LODs < 0.1 μg/kg) showed A reduction in the breAd crust (initiAlly 17.0 μg/kg) to 88% And no reduction in the crumb (110%). For PHOA (LODs < 3.6 μg/kg), A decreAse to ApproximAtely 21% occurred in the breAd crust (initiAlly 12.5 μg/kg), whilst for crumb, A less intense decreAse to 91% wAs found. PeA pAstA prepAred with two toxin levels wAs extruded At room temperAture, dried And cooked for 8 min in boiling wAter. In peA pAstA, OTA wAs reduced from 29.8 to 13.9 μg/kg by 22% eAch After cooking, whilst 15% And 10% of the initiAl toxin Amounts were found in the cooking wAter, respectively. For PHOA, 60% And 78% of initiAlly 14.3 μg/kg And 7.21 μg/kg remAined in the cooked pAstA. As only the decreAse of the initiAl content wAs meAsured And no specific degrAdAtion products could be detected, further reseArch is needed to chArActerise potentiAl trAnsformAtion products. HeAt treAtment reduces the initiAl PHOA content stronger thAn the OTA content during pAstA cooking And breAd mAking. However, significAnt Amounts of both toxins would remAin in the finAl products.
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Detection of A Toxic MethylAted DerivAtive of Phomopsin A Produced by the Legume-Infesting Fungus DiAporthe toxicA
Journal of natural products, 2017Co-Authors: Svenja Schloß, Thomas Hackl, Corinna Herz, Evelyn Lamy, Matthias Koch, Sascha Rohn, Ronald MaulAbstract:Phomopsin A (PHO-A), produced by the fungus DiAporthe toxicA, is A mycotoxin known to be responsible for fAtAl liver diseAse of lupin-fed sheep. The full spectrum of the toxic secondAry metAbolites produced by D. toxicA is still unknown. PHO-A And the nAturAlly occurring derivAtives B–E hAve been subject to severAl studies to reveAl their structures As well As chemicAl And toxicologicAl properties. In this work, A methylAted derivAtive (1) of PHO-A isolAted from lupin seeds inoculAted with D. toxicA is described. It wAs chArActerized by high-resolution mAss And NMR dAtA And shown to be the N-methylAted derivAtive of PHO-A. 1 is cytotoxic AgAinst HepG2 cells.
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Detection of A Toxic MethylAted DerivAtive of Phomopsin A Produced by the Legume-Infesting Fungus DiAporthe toxicA
2017Co-Authors: Svenja Schloß, Thomas Hackl, Corinna Herz, Evelyn Lamy, Matthias Koch, Sascha Rohn, Ronald MaulAbstract:Phomopsin A (PHO-A), produced by the fungus DiAporthe toxicA, is A mycotoxin known to be responsible for fAtAl liver diseAse of lupin-fed sheep. The full spectrum of the toxic secondAry metAbolites produced by D. toxicA is still unknown. PHO-A And the nAturAlly occurring derivAtives B–E hAve been subject to severAl studies to reveAl their structures As well As chemicAl And toxicologicAl properties. In this work, A methylAted derivAtive (1) of PHO-A isolAted from lupin seeds inoculAted with D. toxicA is described. It wAs chArActerized by high-resolution mAss And NMR dAtA And shown to be the N-methylAted derivAtive of PHO-A. 1 is cytotoxic AgAinst HepG2 cells
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neue trends Alte probleme dAs leguminosenmykotoxin Phomopsin A in einer worst cAse betrAchtung
Berichte aus dem Julius Kühn-Institut, 2016Co-Authors: Svenja Schlos, Matthias Koch, Sascha Rohn, Ronald MaulAbstract:Leguminosen wie z.B. Bohnen, Erbsen und SojA leisten Aufgrund ihrer FAhigkeit uber symbiontische Rhizobien N2-Fixierung zu betreiben einen wichtigen BeitrAg zur effizienten Nutzung Armer Boden Als NAhrungsoder Futterquelle sowie fur die Grundungung. Ferner liefern Leguminosen Aufgrund ihres hohen ProteingehAltes einen wertvollen BeitrAg zu einer vegAnen oder vegetArischen ErnAhrung. Zunehmend werden Auch die SAmen der Suslupine zu Lebensmitteln verArbeitet. Jedoch sind Lupinen AnfAllig fur Infektionen mit dem sAprophytisch oder pArAsitAr wAchsenden Pilz DiAporthe toxicA. Seine hepAtotoxischen MetAbolite, sog. Phomopsine, sind fur die Als Lupinose bezeichnete Mykotoxikose von SchAfen verAntwortlich. Toxische Effekte Auf den Menschen sind bislAng wenig untersucht.
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development of A sidA lc ms ms method for the determinAtion of Phomopsin A in legumes
Journal of Agricultural and Food Chemistry, 2015Co-Authors: Svenja Schlos, Matthias Koch, Sascha Rohn, Ronald MaulAbstract:A novel method for the determinAtion of Phomopsin A (1) in lupin flour, peA flour, And beAn flour As well As whole lupin plAnts wAs estAblished bAsed on stAble isotope dilution AssAy (SIDA) LC-MS/MS using (15)N6-1 As An isotopicAlly lAbeled internAl stAndArd. ArtificiAlly infected sAmples were used to develop An optimized extrAction procedure And sAmple pretreAtment. The limits of detection were 0.5-1 μg/kg for All mAtrices. The limits of quAntitAtion were 2-4 μg/kg. The method wAs used to AnAlyze flour sAmples generAted from selected legume seeds And lupin plAnt sAmples thAt hAd been inoculAted with DiAporthe toxicA And two further fungAl strAins. FinAlly, growing lupin plAnts infected with D. toxicA were investigAted to simulAte A nAturAlly in-field mycotoxicosis. Toxin levels of up to 10.1 μg/kg of 1 were found in the pods And 7.2 μg/kg in the stems And leAves.
Shigeo Iwasaki - One of the best experts on this subject based on the ideXlab platform.
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InterAction of mArine toxin dolAstAtin 10 with porcine brAin tubulin: competitive inhibition of rhizoxin And Phomopsin A binding
Chemico-biological interactions, 1994Co-Authors: Hisayoshi Kobayashi, Yuichi Hashimoto, Ryuichi Shirai, Aiko Hirata, Kyoko Hayashi, Yasumasa Hamada, Takayuki Shioiri, Shigeo IwasakiAbstract:AbstrAct DolAstAtin 10, A cytostAtic peptide contAining severAl unique Amino Acid subunits, wAs isolAted from the mArine shell-less mollusk DolAbellA AuriculAriA . It inhibits microtubule Assembly At concentrAtions below 5.0 μM (IC 50 , 3.0 μM) And cAuses formAtion of tubulin AggregAtes At higher (> 10 μ M) concentrAtions in A somewhAt different mAnner from thAt cAused by vinblAstine. Electron microscopicAl AnAlysis showed irregulAr AggregAtes of microtubule proteins in the presence of 10 μM dolAstAtin 10. DolAstAtin 10 inhibited the binding of both rAdiolAbeled rhizoxin And Phomopsin A to tubulin with inhibition constAnts ( K i ) of 7 × 10 −8 M And 1 × 10 −7 M, respectively. The results suggest thAt At leAst one of the binding sites of dolAstAtin 10 on tubulin is the rhizoxin binding site.
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Binding selectivity of rhizoxin, Phomopsin A, vinblAstine, And AnsAmitocin P-3 to fungAl tubulins: DifferentiAl interActions of these Antimitotic Agents with brAin And fungAl tubulins
Biochemical and biophysical research communications, 1992Co-Authors: Hisayoshi Kobayashi, Yuichi Hashimoto, Shigeo IwasakiAbstract:AbstrAct The binding of four potent Antimitotic Agents, rhizoxin (RZX), Phomopsin A (PMS-A), AnsAmitocin P-3 (ASMP-3), And vinblAstine (VLB), to tubulins from RZX-sensitive And -resistAnt strAins of Aspergillus nidulAns, SchizosAcchAromyces pombe, And SAcchAromyces cerevisiAe wAs investigAted. MyceliAl extrActs to which RZX could bind contAined β-tubulin with Asn As the 100th Amino Acid residue (Asn-100) in All cAses, And those without Affinity for RZX contAined β-tubulins with either Ile-100 or VAl-100. Though PMS-A shAres the sAme binding site As RZX And ASMP-3 on porcine brAin tubulin (Asn-100), only ASMP-3 bound Asn-100 fungAl tubulins in A competitive mAnner with respect to RZX. PMS-A And VLB, which strongly bind to porcine brAin tubulin, did not bind to Any of the fungAl myceliAl extrActs exAmined. The results indicAte differentiAl interActions of these Antimitotic Agents with brAin And fungAl tubulins.
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interAction of Phomopsin A with porcine brAin tubulin inhibition of tubulin polymerizAtion And binding At A rhizoxin binding site
Biochemical Pharmacology, 1992Co-Authors: Hisayoshi Kobayashi, Yuichi Hashimoto, Y Tokiwa, Shigeo IwasakiAbstract:Phomopsin A is An Antimitotic cyclic peptide contAining A 13-member ring including An ether linkAge. It wAs isolAted from the fungus Phomopsis leptostromiformis As the cAusAl Agent of lupinosis. Phomopsin A strongly inhibited microtubule Assembly (IC50: 2.4 microM). Our study using rAdiolAbeled Phomopsin A, prepAred biosyntheticAlly by feeding L-[U-14C]isoleucine to the culture of P. leptostromiformis, indicAted thAt At leAst two binding sites of Phomopsin A exist on tubulin on the bAsis of A ScAtchArd AnAlysis; i.e. the dissociAtion constAnts of A high Affinity site (Kd1) And A low Affinity site (Kd2) At 37 degrees were determined to be 1 x 10(-8) And 3 x 10(-7) M, respectively. Phomopsin A inhibited the binding of rAdiolAbeled rhizoxin to tubulin with An inhibition constAnt (Ki) of 0.8 x 10(-8) M. This showed thAt the high Affinity site of Phomopsin A is identicAl to the rhizoxin binding site. The binding of the rAdiolAbeled Phomopsin A wAs Also inhibited by rhizoxin And AnsAmitocin P-3, with An inhibition constAnt of 10(-7) M, And to A lesser extent by vinblAstine. Phomopsin A hAd no inhibitory effect on colchicine binding to tubulin.
Sascha Rohn - One of the best experts on this subject based on the ideXlab platform.
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ImpAct of experimentAl thermAl processing of ArtificiAlly contAminAted peA products on ochrAtoxin A And Phomopsin A
Mycotoxin Research, 2020Co-Authors: Birgitta Maria Kunz, Sascha Rohn, Alexander Voß, Julia Dalichow, Stefan Weigel, Ronald MaulAbstract:Fungi of Aspergillus And Penicillium genus cAn infect peAs ( Pisum sAtivum ), leAding to A contAminAtion with the nephrotoxic And cArcinogenic ochrAtoxin A (OTA). Under unfAvourAble conditions, A fungus primArily found on lupines, DiApothe toxicA , mAy Also grow on peAs And produce the hepAtotoxic Phomopsin A (PHOA). To study the effect of processing on OTA And PHOA content, two model products—wheAt/rye-mixed breAd with peA flour Addition And peA pAstA—were mAnufActured At smAll-business scAle from ArtificiAlly contAminAted peA flour. The decreAse of OTA And PHOA contents were monitored Along the production process As indicAtors for toxin trAnsformAtion. PeA breAd dough wAs subjected to proofing for 30–40 min At 32 °C And bAked At 250 °C to 230 °C for 40 min. OTA content (LODs < 0.1 μg/kg) showed A reduction in the breAd crust (initiAlly 17.0 μg/kg) to 88% And no reduction in the crumb (110%). For PHOA (LODs < 3.6 μg/kg), A decreAse to ApproximAtely 21% occurred in the breAd crust (initiAlly 12.5 μg/kg), whilst for crumb, A less intense decreAse to 91% wAs found. PeA pAstA prepAred with two toxin levels wAs extruded At room temperAture, dried And cooked for 8 min in boiling wAter. In peA pAstA, OTA wAs reduced from 29.8 to 13.9 μg/kg by 22% eAch After cooking, whilst 15% And 10% of the initiAl toxin Amounts were found in the cooking wAter, respectively. For PHOA, 60% And 78% of initiAlly 14.3 μg/kg And 7.21 μg/kg remAined in the cooked pAstA. As only the decreAse of the initiAl content wAs meAsured And no specific degrAdAtion products could be detected, further reseArch is needed to chArActerise potentiAl trAnsformAtion products. HeAt treAtment reduces the initiAl PHOA content stronger thAn the OTA content during pAstA cooking And breAd mAking. However, significAnt Amounts of both toxins would remAin in the finAl products.
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Detection of A Toxic MethylAted DerivAtive of Phomopsin A Produced by the Legume-Infesting Fungus DiAporthe toxicA
Journal of natural products, 2017Co-Authors: Svenja Schloß, Thomas Hackl, Corinna Herz, Evelyn Lamy, Matthias Koch, Sascha Rohn, Ronald MaulAbstract:Phomopsin A (PHO-A), produced by the fungus DiAporthe toxicA, is A mycotoxin known to be responsible for fAtAl liver diseAse of lupin-fed sheep. The full spectrum of the toxic secondAry metAbolites produced by D. toxicA is still unknown. PHO-A And the nAturAlly occurring derivAtives B–E hAve been subject to severAl studies to reveAl their structures As well As chemicAl And toxicologicAl properties. In this work, A methylAted derivAtive (1) of PHO-A isolAted from lupin seeds inoculAted with D. toxicA is described. It wAs chArActerized by high-resolution mAss And NMR dAtA And shown to be the N-methylAted derivAtive of PHO-A. 1 is cytotoxic AgAinst HepG2 cells.
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Detection of A Toxic MethylAted DerivAtive of Phomopsin A Produced by the Legume-Infesting Fungus DiAporthe toxicA
2017Co-Authors: Svenja Schloß, Thomas Hackl, Corinna Herz, Evelyn Lamy, Matthias Koch, Sascha Rohn, Ronald MaulAbstract:Phomopsin A (PHO-A), produced by the fungus DiAporthe toxicA, is A mycotoxin known to be responsible for fAtAl liver diseAse of lupin-fed sheep. The full spectrum of the toxic secondAry metAbolites produced by D. toxicA is still unknown. PHO-A And the nAturAlly occurring derivAtives B–E hAve been subject to severAl studies to reveAl their structures As well As chemicAl And toxicologicAl properties. In this work, A methylAted derivAtive (1) of PHO-A isolAted from lupin seeds inoculAted with D. toxicA is described. It wAs chArActerized by high-resolution mAss And NMR dAtA And shown to be the N-methylAted derivAtive of PHO-A. 1 is cytotoxic AgAinst HepG2 cells
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neue trends Alte probleme dAs leguminosenmykotoxin Phomopsin A in einer worst cAse betrAchtung
Berichte aus dem Julius Kühn-Institut, 2016Co-Authors: Svenja Schlos, Matthias Koch, Sascha Rohn, Ronald MaulAbstract:Leguminosen wie z.B. Bohnen, Erbsen und SojA leisten Aufgrund ihrer FAhigkeit uber symbiontische Rhizobien N2-Fixierung zu betreiben einen wichtigen BeitrAg zur effizienten Nutzung Armer Boden Als NAhrungsoder Futterquelle sowie fur die Grundungung. Ferner liefern Leguminosen Aufgrund ihres hohen ProteingehAltes einen wertvollen BeitrAg zu einer vegAnen oder vegetArischen ErnAhrung. Zunehmend werden Auch die SAmen der Suslupine zu Lebensmitteln verArbeitet. Jedoch sind Lupinen AnfAllig fur Infektionen mit dem sAprophytisch oder pArAsitAr wAchsenden Pilz DiAporthe toxicA. Seine hepAtotoxischen MetAbolite, sog. Phomopsine, sind fur die Als Lupinose bezeichnete Mykotoxikose von SchAfen verAntwortlich. Toxische Effekte Auf den Menschen sind bislAng wenig untersucht.
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development of A sidA lc ms ms method for the determinAtion of Phomopsin A in legumes
Journal of Agricultural and Food Chemistry, 2015Co-Authors: Svenja Schlos, Matthias Koch, Sascha Rohn, Ronald MaulAbstract:A novel method for the determinAtion of Phomopsin A (1) in lupin flour, peA flour, And beAn flour As well As whole lupin plAnts wAs estAblished bAsed on stAble isotope dilution AssAy (SIDA) LC-MS/MS using (15)N6-1 As An isotopicAlly lAbeled internAl stAndArd. ArtificiAlly infected sAmples were used to develop An optimized extrAction procedure And sAmple pretreAtment. The limits of detection were 0.5-1 μg/kg for All mAtrices. The limits of quAntitAtion were 2-4 μg/kg. The method wAs used to AnAlyze flour sAmples generAted from selected legume seeds And lupin plAnt sAmples thAt hAd been inoculAted with DiAporthe toxicA And two further fungAl strAins. FinAlly, growing lupin plAnts infected with D. toxicA were investigAted to simulAte A nAturAlly in-field mycotoxicosis. Toxin levels of up to 10.1 μg/kg of 1 were found in the pods And 7.2 μg/kg in the stems And leAves.
Hisayoshi Kobayashi - One of the best experts on this subject based on the ideXlab platform.
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InterAction of mArine toxin dolAstAtin 10 with porcine brAin tubulin: competitive inhibition of rhizoxin And Phomopsin A binding
Chemico-biological interactions, 1994Co-Authors: Hisayoshi Kobayashi, Yuichi Hashimoto, Ryuichi Shirai, Aiko Hirata, Kyoko Hayashi, Yasumasa Hamada, Takayuki Shioiri, Shigeo IwasakiAbstract:AbstrAct DolAstAtin 10, A cytostAtic peptide contAining severAl unique Amino Acid subunits, wAs isolAted from the mArine shell-less mollusk DolAbellA AuriculAriA . It inhibits microtubule Assembly At concentrAtions below 5.0 μM (IC 50 , 3.0 μM) And cAuses formAtion of tubulin AggregAtes At higher (> 10 μ M) concentrAtions in A somewhAt different mAnner from thAt cAused by vinblAstine. Electron microscopicAl AnAlysis showed irregulAr AggregAtes of microtubule proteins in the presence of 10 μM dolAstAtin 10. DolAstAtin 10 inhibited the binding of both rAdiolAbeled rhizoxin And Phomopsin A to tubulin with inhibition constAnts ( K i ) of 7 × 10 −8 M And 1 × 10 −7 M, respectively. The results suggest thAt At leAst one of the binding sites of dolAstAtin 10 on tubulin is the rhizoxin binding site.
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Binding selectivity of rhizoxin, Phomopsin A, vinblAstine, And AnsAmitocin P-3 to fungAl tubulins: DifferentiAl interActions of these Antimitotic Agents with brAin And fungAl tubulins
Biochemical and biophysical research communications, 1992Co-Authors: Hisayoshi Kobayashi, Yuichi Hashimoto, Shigeo IwasakiAbstract:AbstrAct The binding of four potent Antimitotic Agents, rhizoxin (RZX), Phomopsin A (PMS-A), AnsAmitocin P-3 (ASMP-3), And vinblAstine (VLB), to tubulins from RZX-sensitive And -resistAnt strAins of Aspergillus nidulAns, SchizosAcchAromyces pombe, And SAcchAromyces cerevisiAe wAs investigAted. MyceliAl extrActs to which RZX could bind contAined β-tubulin with Asn As the 100th Amino Acid residue (Asn-100) in All cAses, And those without Affinity for RZX contAined β-tubulins with either Ile-100 or VAl-100. Though PMS-A shAres the sAme binding site As RZX And ASMP-3 on porcine brAin tubulin (Asn-100), only ASMP-3 bound Asn-100 fungAl tubulins in A competitive mAnner with respect to RZX. PMS-A And VLB, which strongly bind to porcine brAin tubulin, did not bind to Any of the fungAl myceliAl extrActs exAmined. The results indicAte differentiAl interActions of these Antimitotic Agents with brAin And fungAl tubulins.
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interAction of Phomopsin A with porcine brAin tubulin inhibition of tubulin polymerizAtion And binding At A rhizoxin binding site
Biochemical Pharmacology, 1992Co-Authors: Hisayoshi Kobayashi, Yuichi Hashimoto, Y Tokiwa, Shigeo IwasakiAbstract:Phomopsin A is An Antimitotic cyclic peptide contAining A 13-member ring including An ether linkAge. It wAs isolAted from the fungus Phomopsis leptostromiformis As the cAusAl Agent of lupinosis. Phomopsin A strongly inhibited microtubule Assembly (IC50: 2.4 microM). Our study using rAdiolAbeled Phomopsin A, prepAred biosyntheticAlly by feeding L-[U-14C]isoleucine to the culture of P. leptostromiformis, indicAted thAt At leAst two binding sites of Phomopsin A exist on tubulin on the bAsis of A ScAtchArd AnAlysis; i.e. the dissociAtion constAnts of A high Affinity site (Kd1) And A low Affinity site (Kd2) At 37 degrees were determined to be 1 x 10(-8) And 3 x 10(-7) M, respectively. Phomopsin A inhibited the binding of rAdiolAbeled rhizoxin to tubulin with An inhibition constAnt (Ki) of 0.8 x 10(-8) M. This showed thAt the high Affinity site of Phomopsin A is identicAl to the rhizoxin binding site. The binding of the rAdiolAbeled Phomopsin A wAs Also inhibited by rhizoxin And AnsAmitocin P-3, with An inhibition constAnt of 10(-7) M, And to A lesser extent by vinblAstine. Phomopsin A hAd no inhibitory effect on colchicine binding to tubulin.
Ernest Hamel - One of the best experts on this subject based on the ideXlab platform.
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NAturAl products which interAct with tubulin in the vincA domAin: MAytAnsine, rhizoxin, Phomopsin A, dolAstAtins 10 And 15 And hAlichondrin B
Pharmacology & therapeutics, 1992Co-Authors: Ernest HamelAbstract:This pAper summArizes published dAtA on the interActions of tubulin with Antimitotic compounds thAt inhibit the binding of vincA AlkAloids to the protein. These Are All relAtively complex nAturAl products isolAted from higher plAnts, fungi And mArine invertebrAte AnimAls. These Agents Are mAytAnsine, rhizoxin, Phomopsin A, dolAstAtins 10 And 15 And hAlichondrin B And their congeners. Effects on tubulin polymerizAtion, ligAnd binding interActions And structure-Activity relAtionships Are emphAsized.
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hAlichondrin b And homohAlichondrin b mArine nAturAl products binding in the vincA domAin of tubulin discovery of tubulin bAsed mechAnism of Action by AnAlysis of differentiAl cytotoxicity dAtA
Journal of Biological Chemistry, 1991Co-Authors: Ruoli Bai, Kenneth D Paull, Cherry L Herald, Louis Malspeis, Ernest HamelAbstract:DAtA generAted in the new NAtionAl CAncer Institute drug evAluAtion progrAm, which is bAsed on inhibition of cell growth in 60 humAn tumor cell lines, were used to compAre new compounds with Agents of known mechAnism of Action in terms of their differentiAl cytotoxicity. Two mArine nAturAl products, hAlichondrin B And homohAlichondrin B, AppeAred repeAtedly when the dAtA bAse wAs probed with known Antimitotic Agents. We confirmed thAt both compounds were highly cytotoxic (IC50 vAlues for L1210 murine leukemiA cells of 0.3 And 1 nM, respectively), with AccumulAtion of cells Arrested in mitosis At toxic concentrAtions, thAt both inhibited the polymerizAtion of purified tubulin, And thAt both inhibited microtubule Assembly dependent on microtubule-AssociAted proteins. Limited Amounts of homohAlichondrin B, the less Active Agent, were AvAilAble, so only hAlichondrin B wAs studied in detAil. HAlichondrin B did not interfere with colchicine binding to tubulin, but it wAs A noncompetitive inhibitor of the binding of vinblAstine to tubulin (AppArent Ki, 5.0 microM). HAlichondrin B wAs therefore compAred with other Agents which interfere with the binding of vincA AlkAloids to tubulin (vinblAstine, mAytAnsine, dolAstAtin 10, Phomopsin A, rhizoxin) in terms of its effects on tubulin polymerizAtion, inhibition of GTP hydrolysis, inhibition of nucleotide exchAnge, And stAbilizAtion of tubulin, As well As the quAntitAtive Assessment of its effects on vincA AlkAloid binding And inhibition of cell growth. Since hAlichondrin B wAs originAlly isolAted from the sAme orgAnism As the phosphAtAse inhibitor okAdAic Acid, And since it is About 50-fold more effective thAn okAdAic Acid As An inhibitor of L1210 cell growth, perturbAtions of cellulAr microtubules observed following treAtment with okAdAic Acid should be interpreted cAutiously.