Neristatin 1 Provides Critical Insight into Bryostatin 1 Structure–Function Relationships
Bryostatin 1, a complex macrocyclic lactone isolated from Bugula neritina, has been the subject of multiple clinical trials for cancer. Although it functions as an activator of protein kinase C (PKC) in vitro, bryostatin 1 paradoxically antagonizes most responses to the prototypical PKC activator, t...
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| Published in | Journal of natural products (Washington, D.C.) Vol. 78; no. 4; pp. 896 - 900 |
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| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
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United States
American Chemical Society and American Society of Pharmacognosy
24.04.2015
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| Abstract | Bryostatin 1, a complex macrocyclic lactone isolated from Bugula neritina, has been the subject of multiple clinical trials for cancer. Although it functions as an activator of protein kinase C (PKC) in vitro, bryostatin 1 paradoxically antagonizes most responses to the prototypical PKC activator, the phorbol esters. The bottom half of the bryostatin 1 structure has been shown to be sufficient to confer binding to PKC. In contrast, we have previously shown that the top half of the bryostatin 1 structure is necessary for its unique biological behavior to antagonize phorbol ester responses. Neristatin 1 comprises a top half similar to that of bryostatin 1 together with a distinct bottom half that confers PKC binding. We report here that neristatin 1 is bryostatin 1-like, not phorbol ester-like, in its biological activity on U937 promyelocytic leukemia cells. We conclude that the top half of the bryostatin 1 structure is largely sufficient for bryostatin 1-like activity, provided the molecule also possesses an appropriate PKC binding domain. |
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| AbstractList | Bryostatin 1, a complex macrocyclic lactone isolated from Bugula neritina, has been the subject of multiple clinical trials for cancer. Although it functions as an activator of protein kinase C (PKC) in vitro, bryostatin 1 paradoxically antagonizes most responses to the prototypical PKC activator, the phorbol esters. The bottom half of the bryostatin 1 structure has been shown to be sufficient to confer binding to PKC. In contrast, we have previously shown that the top half of the bryostatin 1 structure is necessary for its unique biological behavior to antagonize phorbol ester responses. Neristatin 1 comprises a top half similar to that of bryostatin 1 together with a distinct bottom half that confers PKC binding. We report here that neristatin 1 is bryostatin 1-like, not phorbol ester-like, in its biological activity on U937 promyelocytic leukemia cells. We conclude that the top half of the bryostatin 1 structure is largely sufficient for bryostatin 1-like activity, provided the molecule also possesses an appropriate PKC binding domain.Bryostatin 1, a complex macrocyclic lactone isolated from Bugula neritina, has been the subject of multiple clinical trials for cancer. Although it functions as an activator of protein kinase C (PKC) in vitro, bryostatin 1 paradoxically antagonizes most responses to the prototypical PKC activator, the phorbol esters. The bottom half of the bryostatin 1 structure has been shown to be sufficient to confer binding to PKC. In contrast, we have previously shown that the top half of the bryostatin 1 structure is necessary for its unique biological behavior to antagonize phorbol ester responses. Neristatin 1 comprises a top half similar to that of bryostatin 1 together with a distinct bottom half that confers PKC binding. We report here that neristatin 1 is bryostatin 1-like, not phorbol ester-like, in its biological activity on U937 promyelocytic leukemia cells. We conclude that the top half of the bryostatin 1 structure is largely sufficient for bryostatin 1-like activity, provided the molecule also possesses an appropriate PKC binding domain. Bryostatin 1, a complex macrocyclic lactone isolated from Bugula neritina, has been the subject of multiple clinical trials for cancer. Although it functions as an activator of protein kinase C (PKC) in vitro, bryostatin 1 paradoxically antagonizes most responses to the prototypical PKC activator, the phorbol esters. The bottom half of the bryostatin 1 structure has been shown to be sufficient to confer binding to PKC. In contrast, we have previously shown that the top half of the bryostatin 1 structure is necessary for its unique biological behavior to antagonize phorbol ester responses. Neristatin 1 comprises a top half similar to that of bryostatin 1 together with a distinct bottom half that confers PKC binding. We report here that neristatin 1 is bryostatin 1-like, not phorbol ester-like, in its biological activity on U937 promyelocytic leukemia cells. We conclude that the top half of the bryostatin 1 structure is largely sufficient for bryostatin 1-like activity, provided the molecule also possesses an appropriate PKC binding domain. Bryostatin 1, a complex macrocyclic lactone isolated from Bugula neritina , has been the subject of multiple clinical trials for cancer. Although it functions as an activator of protein kinase C (PKC) in vitro , bryostatin 1 paradoxically antagonizes most responses to the prototypical PKC activator, the phorbol esters. The bottom half of the bryostatin 1 structure has been shown to be sufficient to confer binding to PKC. In contrast, we have previously shown that the top half of the bryostatin 1 structure is necessary for its unique biological behavior to antagonize phorbol ester responses. Neristatin 1 comprises a top half similar to that of bryostatin 1 together with a distinct bottom half that confers PKC binding. We report here that neristatin 1 is bryostatin 1-like, not phorbol ester-like, in its biological activity on U937 promyelocytic leukemia cells. We conclude that the top half of the bryostatin 1 structure is largely sufficient for bryostatin 1-like activity, provided the molecule also possesses an appropriate PKC binding domain. |
| Author | Melody, Noeleen Kedei, Noemi Keck, Gary E Kraft, Matthew B Herald, Cherry L Pettit, George R Blumberg, Peter M |
| AuthorAffiliation | Department of Chemistry Department of Chemistry and Biochemistry Arizona State University Laboratory of Cancer Biology and Genetics, Center for Cancer Research National Cancer Institute University of Utah |
| AuthorAffiliation_xml | – name: University of Utah – name: Department of Chemistry – name: Laboratory of Cancer Biology and Genetics, Center for Cancer Research – name: National Cancer Institute – name: Arizona State University – name: Department of Chemistry and Biochemistry |
| Author_xml | – sequence: 1 givenname: Noemi surname: Kedei fullname: Kedei, Noemi – sequence: 2 givenname: Matthew B surname: Kraft fullname: Kraft, Matthew B – sequence: 3 givenname: Gary E surname: Keck fullname: Keck, Gary E – sequence: 4 givenname: Cherry L surname: Herald fullname: Herald, Cherry L – sequence: 5 givenname: Noeleen surname: Melody fullname: Melody, Noeleen – sequence: 6 givenname: George R surname: Pettit fullname: Pettit, George R – sequence: 7 givenname: Peter M surname: Blumberg fullname: Blumberg, Peter M email: blumberp@dc37a.nci.nih.gov |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25808573$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1021/ja5078188 10.1042/BST20140172 10.1016/j.drudis.2013.10.013 10.1002/asia.200900634 10.1021/jm010258f 10.2174/092986712800493020 10.1021/ja507825s 10.1021/np400947d 10.1021/cb300671s 10.1152/ajplung.2000.279.3.L429 10.1002/cbic.201100064 10.1021/ja110198y 10.1021/ja00388a092 10.1016/j.bcp.2011.03.018 10.2741/3385 10.1021/cr900019j 10.1093/carcin/8.9.1343 10.1016/j.bcp.2012.10.028 10.1016/j.bmcl.2013.12.059 10.2174/138945008785132376 10.1002/(SICI)1098-1128(199909)19:5<388::AID-MED6>3.0.CO;2-H 10.1074/jbc.272.52.33338 10.1002/anie.201101562 10.1039/b009211h 10.1021/np9604386 10.1248/cpb.47.1134 10.1021/np5000796 10.1016/0092-8674(95)90011-X 10.1021/ja8022169 10.1021/ar700155p 10.1007/s11101-009-9123-y 10.1021/ja00017a062 10.1002/anie.201001200 10.1038/nrc2110 10.1016/S0065-230X(08)60799-X |
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| References | Shao L. (ref19/cit19) 2001; 44 Cragg G. M. (ref1/cit1) 2014; 77 Hennings H. (ref23/cit23) 1987; 8 Fujiki H. (ref18/cit18) 1987; 49 Manaviazar S. (ref25/cit25) 2011; 50 Blumberg P. M. (ref17/cit17) 2008; 9 Kraft M. B. (ref33/cit33) 2014; 136 Antal C. E. (ref13/cit13) 2014; 42 Pettit G. R. (ref6/cit6) 2014; 77 Hecker E. (ref20/cit20) 1968; 28 Kedei N. (ref22/cit22) 2011; 12 Pettit G. R. (ref10/cit10) 1982; 104 Kimura K. (ref39/cit39) 1999; 47 Zhang G. (ref16/cit16) 1995; 81 Kedei N. (ref35/cit35) 2013; 85 Pettit G. R. (ref11/cit11) 1991; 57 Hale K. J. (ref27/cit27) 2010; 5 Cragg G. M. (ref3/cit3) 2009; 109 Kinghorn A. D. (ref8/cit8) 2009; 12 Pettit G. R. (ref31/cit31) 1991; 113 Griner E. M. (ref14/cit14) 2007; 7 Ruan B. F. (ref21/cit21) 2012; 19 Hale K. J. (ref28/cit28) 2002; 19 Cragg G. M. (ref4/cit4) 1994; 185 Pettit G. R. (ref9/cit9) 1996; 59 Cragg G. M. (ref5/cit5) 2009; 8 Brown D. G. (ref2/cit2) 2014; 24 Dempsey E. C. (ref12/cit12) 2000; 279 Kedei N. (ref36/cit36) 2011; 81 Keck G. E. (ref30/cit30) 2008; 130 Pascolutti M. (ref7/cit7) 2014; 19 Keck G. E. (ref32/cit32) 2010; 49 Reyland M. E. (ref15/cit15) 2009; 14 Andrews I. P. (ref37/cit37) 2014; 136 Wender P. A. (ref26/cit26) 2008; 41 Kedei N. (ref34/cit34) 2013; 8 Wender P. A. (ref29/cit29) 1999; 19 Keck G. E. (ref24/cit24) 2011; 133 Lorenzo P. S. (ref38/cit38) 1997; 272 12195811 - Nat Prod Rep. 2002 Aug;19(4):413-53 3621472 - Carcinogenesis. 1987 Sep;8(9):1343-6 20491108 - Angew Chem Int Ed Engl. 2010 Jun 21;49(27):4580-4 8792630 - J Nat Prod. 1996 Aug;59(8):812-21 9407126 - J Biol Chem. 1997 Dec 26;272(52):33338-43 10502742 - Med Res Rev. 1999 Sep;19(5):388-407 25207655 - J Am Chem Soc. 2014 Sep 24;136(38):13209-16 2890278 - Adv Cancer Res. 1987;49:223-64 21458422 - Biochem Pharmacol. 2011 Jun 1;81(11):1296-308 23369356 - ACS Chem Biol. 2013 Apr 19;8(4):767-77 5723975 - Cancer Res. 1968 Nov;28(11):2338-49 25207434 - J Am Chem Soc. 2014 Sep 24;136(38):13202-8 7736854 - Ciba Found Symp. 1994;185:178-90; discussion 190-6 18159936 - Acc Chem Res. 2008 Jan;41(1):40-9 19273207 - Front Biosci (Landmark Ed). 2009;14:2386-99 19333864 - Curr Opin Drug Discov Devel. 2009 Mar;12(2):189-96 24171951 - Drug Discov Today. 2014 Mar;19(3):215-21 10956616 - Am J Physiol Lung Cell Mol Physiol. 2000 Sep;279(3):L429-38 21751307 - Angew Chem Int Ed Engl. 2011 Sep 12;50(38):8786-9 25399557 - Biochem Soc Trans. 2014 Dec;42(6):1477-83 7781068 - Cell. 1995 Jun 16;81(6):917-24 17384583 - Nat Rev Cancer. 2007 Apr;7(4):281-94 18452293 - J Am Chem Soc. 2008 May 28;130(21):6660-1 18691011 - Curr Drug Targets. 2008 Aug;9(8):641-52 24388805 - Bioorg Med Chem Lett. 2014 Jan 15;24(2):413-8 21542090 - Chembiochem. 2011 May 16;12(8):1242-51 24499205 - J Nat Prod. 2014 Mar 28;77(3):703-23 11689073 - J Med Chem. 2001 Nov 8;44(23):3872-80 22506770 - Curr Med Chem. 2012;19(16):2652-64 23146662 - Biochem Pharmacol. 2013 Feb 1;85(3):313-24 19422222 - Chem Rev. 2009 Jul;109(7):3012-43 21175177 - J Am Chem Soc. 2011 Feb 2;133(4):744-7 20354984 - Chem Asian J. 2010 Apr 1;5(4):704-54 24694263 - J Nat Prod. 2014 Apr 25;77(4):863-72 1937312 - Fortschr Chem Org Naturst. 1991;57:153-195 |
| References_xml | – volume: 136 start-page: 13202 year: 2014 ident: ref33/cit33 publication-title: J. Am. Chem. Soc. doi: 10.1021/ja5078188 – volume: 12 start-page: 189 year: 2009 ident: ref8/cit8 publication-title: Curr. Opin. Drug Discovery Dev. – volume: 42 start-page: 1477 year: 2014 ident: ref13/cit13 publication-title: Biochem. Soc. Trans. doi: 10.1042/BST20140172 – volume: 185 start-page: 178 year: 1994 ident: ref4/cit4 publication-title: Ciba Found. Symp. – volume: 19 start-page: 215 year: 2014 ident: ref7/cit7 publication-title: Drug Discovery Today doi: 10.1016/j.drudis.2013.10.013 – volume: 5 start-page: 704 year: 2010 ident: ref27/cit27 publication-title: Chem.—Asian J. doi: 10.1002/asia.200900634 – volume: 44 start-page: 3872 year: 2001 ident: ref19/cit19 publication-title: J. Med. Chem. doi: 10.1021/jm010258f – volume: 19 start-page: 2652 year: 2012 ident: ref21/cit21 publication-title: Curr. Med. Chem. doi: 10.2174/092986712800493020 – volume: 136 start-page: 13209 year: 2014 ident: ref37/cit37 publication-title: J. Am. Chem. Soc. doi: 10.1021/ja507825s – volume: 77 start-page: 863 year: 2014 ident: ref6/cit6 publication-title: J. Nat. Prod. doi: 10.1021/np400947d – volume: 8 start-page: 767 year: 2013 ident: ref34/cit34 publication-title: ACS Chem. Biol. doi: 10.1021/cb300671s – volume: 279 start-page: 429 year: 2000 ident: ref12/cit12 publication-title: Am. J. Lung Cell Mol. Physiol. doi: 10.1152/ajplung.2000.279.3.L429 – volume: 12 start-page: 1242 year: 2011 ident: ref22/cit22 publication-title: ChemBioChem doi: 10.1002/cbic.201100064 – volume: 133 start-page: 744 year: 2011 ident: ref24/cit24 publication-title: J. Am. Chem. Soc. doi: 10.1021/ja110198y – volume: 104 start-page: 6846 year: 1982 ident: ref10/cit10 publication-title: J. Am. Chem. Soc. doi: 10.1021/ja00388a092 – volume: 81 start-page: 1296 year: 2011 ident: ref36/cit36 publication-title: Biochem. Pharmacol. doi: 10.1016/j.bcp.2011.03.018 – volume: 14 start-page: 2386 year: 2009 ident: ref15/cit15 publication-title: Front. Biosci. doi: 10.2741/3385 – volume: 57 start-page: 153 year: 1991 ident: ref11/cit11 publication-title: Fortschr. Chem. Org. Naturst. – volume: 109 start-page: 3012 year: 2009 ident: ref3/cit3 publication-title: Chem. Rev. doi: 10.1021/cr900019j – volume: 8 start-page: 1343 year: 1987 ident: ref23/cit23 publication-title: Carcinogenesis doi: 10.1093/carcin/8.9.1343 – volume: 85 start-page: 313 year: 2013 ident: ref35/cit35 publication-title: Biochem. Pharmacol. doi: 10.1016/j.bcp.2012.10.028 – volume: 24 start-page: 413 year: 2014 ident: ref2/cit2 publication-title: Bioorg. Med. Chem. Lett. doi: 10.1016/j.bmcl.2013.12.059 – volume: 9 start-page: 641 year: 2008 ident: ref17/cit17 publication-title: Curr. Drug Targets doi: 10.2174/138945008785132376 – volume: 19 start-page: 388 year: 1999 ident: ref29/cit29 publication-title: Med. Res. Rev. doi: 10.1002/(SICI)1098-1128(199909)19:5<388::AID-MED6>3.0.CO;2-H – volume: 272 start-page: 33338 year: 1997 ident: ref38/cit38 publication-title: J. Biol. Chem. doi: 10.1074/jbc.272.52.33338 – volume: 50 start-page: 8786 year: 2011 ident: ref25/cit25 publication-title: Angew. Chem., Int. Ed. doi: 10.1002/anie.201101562 – volume: 19 start-page: 413 year: 2002 ident: ref28/cit28 publication-title: Nat. Prod. Rep. doi: 10.1039/b009211h – volume: 59 start-page: 812 year: 1996 ident: ref9/cit9 publication-title: J. Nat. Prod. doi: 10.1021/np9604386 – volume: 47 start-page: 1134 year: 1999 ident: ref39/cit39 publication-title: Chem. Pharm. Bull. doi: 10.1248/cpb.47.1134 – volume: 77 start-page: 703 year: 2014 ident: ref1/cit1 publication-title: J. Nat. Prod. doi: 10.1021/np5000796 – volume: 81 start-page: 917 year: 1995 ident: ref16/cit16 publication-title: Cell doi: 10.1016/0092-8674(95)90011-X – volume: 28 start-page: 2338 year: 1968 ident: ref20/cit20 publication-title: Cancer Res. – volume: 130 start-page: 6660 year: 2008 ident: ref30/cit30 publication-title: J. Am. Chem. Soc. doi: 10.1021/ja8022169 – volume: 41 start-page: 40 year: 2008 ident: ref26/cit26 publication-title: Acc. Chem. Res. doi: 10.1021/ar700155p – volume: 8 start-page: 313 year: 2009 ident: ref5/cit5 publication-title: Phytochem. Rev. doi: 10.1007/s11101-009-9123-y – volume: 113 start-page: 6693 year: 1991 ident: ref31/cit31 publication-title: J. Am. Chem. Soc. doi: 10.1021/ja00017a062 – volume: 49 start-page: 4580 year: 2010 ident: ref32/cit32 publication-title: Angew. Chem., Int. Ed. doi: 10.1002/anie.201001200 – volume: 7 start-page: 281 year: 2007 ident: ref14/cit14 publication-title: Nat. Rev. Cancer doi: 10.1038/nrc2110 – volume: 49 start-page: 223 year: 1987 ident: ref18/cit18 publication-title: Adv. Cancer Res. doi: 10.1016/S0065-230X(08)60799-X – reference: 19422222 - Chem Rev. 2009 Jul;109(7):3012-43 – reference: 5723975 - Cancer Res. 1968 Nov;28(11):2338-49 – reference: 21175177 - J Am Chem Soc. 2011 Feb 2;133(4):744-7 – reference: 24171951 - Drug Discov Today. 2014 Mar;19(3):215-21 – reference: 1937312 - Fortschr Chem Org Naturst. 1991;57:153-195 – reference: 18452293 - J Am Chem Soc. 2008 May 28;130(21):6660-1 – reference: 25207434 - J Am Chem Soc. 2014 Sep 24;136(38):13202-8 – reference: 18691011 - Curr Drug Targets. 2008 Aug;9(8):641-52 – reference: 20491108 - Angew Chem Int Ed Engl. 2010 Jun 21;49(27):4580-4 – reference: 2890278 - Adv Cancer Res. 1987;49:223-64 – reference: 24388805 - Bioorg Med Chem Lett. 2014 Jan 15;24(2):413-8 – reference: 10502742 - Med Res Rev. 1999 Sep;19(5):388-407 – reference: 24499205 - J Nat Prod. 2014 Mar 28;77(3):703-23 – reference: 8792630 - J Nat Prod. 1996 Aug;59(8):812-21 – reference: 24694263 - J Nat Prod. 2014 Apr 25;77(4):863-72 – reference: 10956616 - Am J Physiol Lung Cell Mol Physiol. 2000 Sep;279(3):L429-38 – reference: 3621472 - Carcinogenesis. 1987 Sep;8(9):1343-6 – reference: 7736854 - Ciba Found Symp. 1994;185:178-90; discussion 190-6 – reference: 20354984 - Chem Asian J. 2010 Apr 1;5(4):704-54 – reference: 11689073 - J Med Chem. 2001 Nov 8;44(23):3872-80 – reference: 22506770 - Curr Med Chem. 2012;19(16):2652-64 – reference: 19333864 - Curr Opin Drug Discov Devel. 2009 Mar;12(2):189-96 – reference: 21751307 - Angew Chem Int Ed Engl. 2011 Sep 12;50(38):8786-9 – reference: 19273207 - Front Biosci (Landmark Ed). 2009;14:2386-99 – reference: 21458422 - Biochem Pharmacol. 2011 Jun 1;81(11):1296-308 – reference: 23369356 - ACS Chem Biol. 2013 Apr 19;8(4):767-77 – reference: 7781068 - Cell. 1995 Jun 16;81(6):917-24 – reference: 23146662 - Biochem Pharmacol. 2013 Feb 1;85(3):313-24 – reference: 25399557 - Biochem Soc Trans. 2014 Dec;42(6):1477-83 – reference: 18159936 - Acc Chem Res. 2008 Jan;41(1):40-9 – reference: 21542090 - Chembiochem. 2011 May 16;12(8):1242-51 – reference: 25207655 - J Am Chem Soc. 2014 Sep 24;136(38):13209-16 – reference: 9407126 - J Biol Chem. 1997 Dec 26;272(52):33338-43 – reference: 17384583 - Nat Rev Cancer. 2007 Apr;7(4):281-94 – reference: 12195811 - Nat Prod Rep. 2002 Aug;19(4):413-53 |
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| Snippet | Bryostatin 1, a complex macrocyclic lactone isolated from Bugula neritina, has been the subject of multiple clinical trials for cancer. Although it functions... Bryostatin 1, a complex macrocyclic lactone isolated from Bugula neritina , has been the subject of multiple clinical trials for cancer. Although it functions... |
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| SubjectTerms | Animals bioactive properties Bryostatins - chemistry Bryozoa - chemistry clinical trials esters Humans Models, Molecular Molecular Structure neoplasm cells neoplasms Neritina Phorbol Esters protein kinase C Protein Kinase C - drug effects Protein Kinase C - metabolism structure-activity relationships |
| Title | Neristatin 1 Provides Critical Insight into Bryostatin 1 Structure–Function Relationships |
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