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Bryostatin

January 01, 1970

Bryostatins are a group of macrolide lactones from (bacterial symbionts of) the marine organism Bugula neritina that were first collected and provided to JL Hartwell’s anticancer drug discovery group at the National Cancer Institute (NCI) by Jack Rudloe.[1] Bryostatins are potent modulators of protein kinase C. They have been studied in clinical trials as anti-cancer agents, as anti-AIDS/HIV agents and in people with Alzheimer's disease.

Bryostatin 1
Names
IUPAC name
(1S,3S,5Z,7R,8E,11S,12S,13E,15S,17R,20R,23R,25S)-25-Acetoxy-1,11,20-trihydroxy-17-[(1R)-1-hydroxyethyl]-5,13-bis(2-methoxy-2-oxoethylidene)-10,10,26,26-tetramethyl-19-oxo-18,27,28,29-tetraoxatetracyclo[21.3.1.13,7.111,15]nonacos-8-en-12-yl (2E,4E)-2,4-octadienoate
Identifiers
  • 1: 83314-01-6
3D model (JSmol)
  • 1: Interactive image
ChEBI
  • 1: CHEBI:88353
ChEMBL
  • 1: ChEMBL449158
ChemSpider
  • 1: 27022418
DrugBank
  • 1: DB11752
KEGG
  • 1: C05149
  • 1: 5280757
UNII
  • 1: 37O2X55Y9E
  • InChI=1S/C47H68O17/c1-10-11-12-13-14-15-39(51)62-42-31(24-41(53)58-9)23-34-25-37(28(2)48)61-43(54)36(50)17-16-33-26-38(59-29(3)49)45(6,7)46(55,63-33)27-35-21-30(22-40(52)57-8)20-32(60-35)18-19-44(4,5)47(42,56)64-34/h12-15,18-19,22,24,28,32-38,42,48,50,55-56H,10-11,16-17,20-21,23,25-27H2,1-9H3/b13-12+,15-14+,19-18+,30-22+,31-24+/t28-,32+,33-,34+,35+,36-,37-,38+,42+,46+,47-/m1/s1
    Key: XYXASLYZTKBYQJ-OAUMSBLFSA-N
  • 1: InChI=1/C47H68O17/c1-10-11-12-13-14-15-39(51)62-42-31(24-41(53)58-9)23-34-25-37(28(2)48)61-43(54)36(50)17-16-33-26-38(59-29(3)49)45(6,7)46(55,63-33)27-35-21-30(22-40(52)57-8)20-32(60-35)18-19-44(4,5)47(42,56)64-34/h12-15,18-19,22,24,28,32-38,42,48,50,55-56H,10-11,16-17,20-21,23,25-27H2,1-9H3/b13-12+,15-14+,19-18+,30-22+,31-24+/t28-,32+,33-,34+,35+,36-,37-,38+,42+,46+,47-/m1/s1
    Key: XYXASLYZTKBYQJ-OAUMSBLFBY
  • 1: CCC/C=C/C=C/C(=O)O[C@H]1/C(=C/C(=O)OC)/C[C@H]2C[C@@H](OC(=O)[C@@H](CC[C@@H]3C[C@@H](C([C@@](O3)(C[C@@H]4C/C(=C/C(=O)OC)/C[C@@H](O4)/C=C/C([C@@]1(O2)O)(C)C)O)(C)C)OC(=O)C)O)[C@@H](C)O
Properties
C47H68O17
Molar mass 905.044 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Biological effects edit

Bryostatin 1 is a potent modulator of protein kinase C (PKC).[2]

It showed activity in laboratory tests in cells and model animals, so it was brought into clinical trials. As of 2014 over thirty clinical trials had been conducted, using bryostatin alone and in combination with other agents, in both solid tumors and blood tumors; it did not show a good enough risk:benefit ratio to be advanced further.[3]

It showed enough promise in animal models of Alzheimer's disease that a Phase II trial was started by 2010;[4] the trial was sponsored by the Blanchette Rockefeller Neurosciences Institute.[5] Scientists from that institute started a company called Neurotrope,[6] and launched another clinical trial in Alzheimer's disease,[7] preliminary results of which were released in 2017. [8][9]

Bryostatin has also been studied in people with HIV.[2]

Chemistry edit

Bryostatin 1 was first isolated in the 1960s by George Pettit from extracts of a species of bryozoan, Bugula neritina, based on research from samples originally provided by Jack Rudloe to Jonathan L. Hartwell’s anticancer drug discovery group at the National Cancer Institute (NCI).[1] The structure of bryostatin 1 was determined in 1982.[10] As of 2010 20 different bryostatins had been isolated.[11]

The low concentration in bryozoans (to extract one gram of bryostatin, roughly one tonne of the raw bryozoans is needed) makes extraction unviable for large scale production. Due to the structural complexity, total synthesis has proved difficult, with only a few total syntheses reported so far. Total syntheses have been published for bryostatins 1, 2, 3, 7, 9 and 16.[12][13][14][15][16][17][18][19] Among them, Wender’s total synthesis of bryostatin 1 [19] is the shortest synthesis of any bryostatin reported, to date.

A number of structurally simpler synthetic analogs also have been prepared which exhibit similar biological profile and in some cases greater potency, which may provide a practical supply for clinical use.[20]

Biosynthesis edit

 
B. Neritina biosynthetic pathway for bryostatins.

In B. Neritina, bryostatin biosynthesis is carried out through a type I polyketide synthase cluster, bry. BryR is the secondary metabolism homolog of HMG-CoA synthase, which is the PKS in bacterial primary metabolism. In the bryostatin pathway, the BryR module catalyzes β-Branching between a local acetoacetyl acceptor acyl carrier protein (ACP-a) and an appropriate donor BryU acetyl-ACP (ACP-d).[21]

The first step involves the loading of a malonyl unit onto a discrete BryU ACP-d within an initial BryA module. The extended BryU product in BryA is then loaded onto a cysteine sidechain of BryR for interaction with ACP-a. Upon interaction, BryR then catalyzes β-Branching, facilitating an aldol reaction between the alpha-carbon of the BryU unit and the β-ketone of ACP-a, yielding a product similar to HMGS products in primary metabolism. After β-Branching, subsequent dehydration by a BryT enoyl-CoA hydratase homolog (ECH), as well as BryA O-methylation and BryB double bond isomerization of the generated HMGS product, are carried out in specific domains of the bry cluster. These post-β-Branching steps generate the vinyl methylester moieties which are found in all natural product bryostatins. Finally, BryC and BryD are responsible for further extension, pyran ring closure, and cyclization of the HMGS product to produce the novel bryostatin product.[22]

In the presence of BryR, ACP-d conversion to holo-ACP-d was observed prior to β-Branching. BryR was shown to have high specificity for ACP-d only after this conversion. Specificity for these protein-bound groups is a feature that differentiates the HMGS homologs found in primary metabolism, where HMGS typically acts on substrates linked to Coenzyme A, from those found in non-ribosomal peptide synthase (NRPS) or PKS pathways such as the bryostatin pathway.[21]

References edit

  1. ^ a b Halford B (24 October 2011). "The Bryostatins' Tale". Chemical and Engineering News. 89 (43): 10–17. doi:10.1021/cen-v089n043.p010.
  2. ^ a b Kollár P, Rajchard J, Balounová Z, Pazourek J (February 2014). "Marine natural products: bryostatins in preclinical and clinical studies". Pharmaceutical Biology. 52 (2): 237–42. doi:10.3109/13880209.2013.804100. PMID 24033119.
  3. ^ name=Kollar2014rev>Kollár P, Rajchard J, Balounová Z, Pazourek J (February 2014). "Marine natural products: bryostatins in preclinical and clinical studies". Pharmaceutical Biology. 52 (2): 237–42. doi:10.3109/13880209.2013.804100. PMID 24033119.
  4. ^ Trindade-Silva AE, Lim-Fong GE, Sharp KH, Haygood MG (December 2010). "Bryostatins: biological context and biotechnological prospects". Current Opinion in Biotechnology. 21 (6): 834–42. doi:10.1016/j.copbio.2010.09.018. PMC 4497553. PMID 20971628.
  5. ^ Clinical trial number NCT00606164 for "Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics Study of Bryostatin 1 in Patients With Alzheimer's Disease" at ClinicalTrials.gov
  6. ^ "Alzheimer's Researchers Discover Bryostatin Can Slow, Reverse Disease Progression". Alzheimer's News Today. 19 August 2014.
  7. ^ Clinical trial number NCT02431468 for "A Study Assessing Bryostatin in the Treatment of Moderately Severe to Severe Alzheimer's Disease" at ClinicalTrials.gov
  8. ^ Taylor NP (May 1, 2017). "Neurotrope misses primary endpoint in Alzheimer's trial". FierceBiotech.
  9. ^ Nelson TJ, Sun MK, Lim C, Sen A, Khan T, Chirila FV, Alkon DL (2017). "Bryostatin Effects on Cognitive Function and PKCɛ in Alzheimer's Disease Phase IIa and Expanded Access Trials". Journal of Alzheimer's Disease. 58 (2): 521–535. doi:10.3233/JAD-170161. PMC 5438479. PMID 28482641.
  10. ^ Pettit GR, Cherry Herald L, Doubek DL, Herald DL, Arnold E, Clardy J (1982). "Isolation and structure of bryostatin 1". J. Am. Chem. Soc. 104 (24): 6846–6848. doi:10.1021/ja00388a092.
  11. ^ Hale KJ, Manaviazar S (April 2010). "New approaches to the total synthesis of the bryostatin antitumor macrolides". Chemistry: An Asian Journal. 5 (4): 704–54. doi:10.1002/asia.200900634. PMID 20354984.
  12. ^ Keck GE, Poudel YB, Cummins TJ, Rudra A, Covel JA (February 2011). "Total synthesis of bryostatin 1". Journal of the American Chemical Society. 133 (4): 744–7. doi:10.1021/ja110198y. PMC 3030632. PMID 21175177.
  13. ^ Evans DA, Carter PH, Carreira EM, Charette AB, Prunet JA, Lautens M (1999). "Total Synthesis of Bryostatin 2". J. Am. Chem. Soc. 121 (33): 7540–7552. doi:10.1021/ja990860j.
  14. ^ Ohmori K, Ogawa Y, Obitsu T, Ishikawa Y, Nishiyama S, Yamamura S (July 2000). "Total Synthesis of Bryostatin". Angewandte Chemie. 39 (13): 2290–2294. doi:10.1002/1521-3773(20000703)39:13<2290::AID-ANIE2290>3.0.CO;2-6. PMID 10941067.
  15. ^ Kageyama M, Tamura T, Nantz MH, Roberts JC, Somfai P, Whritenour DC, Masamune S (1990). "Synthesis of Bryostatin 7". J. Am. Chem. Soc. 112 (20): 7407–7408. doi:10.1021/ja00176a058.
  16. ^ Lu Y, Woo SK, Krische MJ (September 2011). "Total synthesis of bryostatin 7 via C-C bond-forming hydrogenation". Journal of the American Chemical Society. 133 (35): 13876–9. doi:10.1021/ja205673e. PMC 3164899. PMID 21780806.
  17. ^ Wender PA, Schrier AJ (June 2011). "Total synthesis of bryostatin 9". Journal of the American Chemical Society. 133 (24): 9228–31. doi:10.1021/ja203034k. PMC 3129979. PMID 21618969.
  18. ^ Trost BM, Dong G (November 2008). "Total synthesis of bryostatin 16 using atom-economical and chemoselective approaches". Nature. 456 (7221): 485–8. Bibcode:2008Natur.456..485T. doi:10.1038/nature07543. PMC 2728752. PMID 19037312.
  19. ^ a b Wender PA, Hardman CT, Ho S, Jeffreys MS, Maclaren JK, Quiroz RV, Ryckbosch SM, Shimizu AJ, Sloane JL, Stevens MC (October 2017). "Scalable synthesis of bryostatin 1 and analogs, adjuvant leads against latent HIV". Science. 358 (6360): 218–223. Bibcode:2017Sci...358..218W. doi:10.1126/science.aan7969. PMC 5714505. PMID 29026042.
  20. ^ Wender PA, Baryza JL, Bennett CE, Bi FC, Brenner SE, Clarke MO, Horan JC, Kan C, Lacôte E, Lippa B, Nell PG, Turner TM (November 2002). "The practical synthesis of a novel and highly potent analogue of bryostatin". Journal of the American Chemical Society. 124 (46): 13648–9. doi:10.1021/ja027509+. PMID 12431074.
  21. ^ a b Buchholz TJ, Rath CM, Lopanik NB, Gardner NP, Håkansson K, Sherman DH (October 2010). "Polyketide β-branching in bryostatin biosynthesis: identification of surrogate acetyl-ACP donors for BryR, an HMG-ACP synthase". Chemistry & Biology. 17 (10): 1092–100. doi:10.1016/j.chembiol.2010.08.008. PMC 2990979. PMID 21035732.
  22. ^ Slocum ST, Lowell AN, Tripathi AN, Shende VV, Smith JL, Sherman DH (2018). "Chemoenzymatic Dissection of Polyketide β-Branching in the Bryostatin Pathway". Marine Enzymes and Specialized Metabolism - Part A. Methods in Enzymology. Vol. 604. pp. 207–236. doi:10.1016/bs.mie.2018.01.034. ISBN 9780128139592. PMC 6327954. PMID 29779653.

Further reading edit

  • Proksch P, Edrada RA, Ebel R (July 2002). "Drugs from the seas - current status and microbiological implications". Applied Microbiology and Biotechnology. 59 (2–3): 125–34. doi:10.1007/s00253-002-1006-8. PMID 12111137. S2CID 29833324.

External links edit

  • Kilham C. . Fox News Health. Archived from the original on 25 April 2012.
  • . Aphios Corporation. Archived from the original on 2013-12-20. Retrieved 2013-12-19.
  • . Aphios Corporation. Archived from the original on 2012-11-12. Retrieved 2013-12-19.
  • . Aphios Corporation. Archived from the original on 2013-12-20. Retrieved 2013-12-19.

January 01, 1970
bryostatin, group, macrolide, lactones, from, bacterial, symbionts, marine, organism, bugula, neritina, that, were, first, collected, provided, hartwell, anticancer, drug, discovery, group, national, cancer, institute, jack, rudloe, potent, modulators, protein. Bryostatins are a group of macrolide lactones from bacterial symbionts of the marine organism Bugula neritina that were first collected and provided to JL Hartwell s anticancer drug discovery group at the National Cancer Institute NCI by Jack Rudloe 1 Bryostatins are potent modulators of protein kinase C They have been studied in clinical trials as anti cancer agents as anti AIDS HIV agents and in people with Alzheimer s disease Bryostatin 1 Names IUPAC name 1S 3S 5Z 7R 8E 11S 12S 13E 15S 17R 20R 23R 25S 25 Acetoxy 1 11 20 trihydroxy 17 1R 1 hydroxyethyl 5 13 bis 2 methoxy 2 oxoethylidene 10 10 26 26 tetramethyl 19 oxo 18 27 28 29 tetraoxatetracyclo 21 3 1 13 7 111 15 nonacos 8 en 12 yl 2E 4E 2 4 octadienoate Identifiers CAS Number 1 83314 01 6 3D model JSmol 1 Interactive image ChEBI 1 CHEBI 88353 ChEMBL 1 ChEMBL449158 ChemSpider 1 27022418 DrugBank 1 DB11752 KEGG 1 C05149 PubChem CID 1 5280757 UNII 1 37O2X55Y9E InChI InChI 1S C47H68O17 c1 10 11 12 13 14 15 39 51 62 42 31 24 41 53 58 9 23 34 25 37 28 2 48 61 43 54 36 50 17 16 33 26 38 59 29 3 49 45 6 7 46 55 63 33 27 35 21 30 22 40 52 57 8 20 32 60 35 18 19 44 4 5 47 42 56 64 34 h12 15 18 19 22 24 28 32 38 42 48 50 55 56H 10 11 16 17 20 21 23 25 27H2 1 9H3 b13 12 15 14 19 18 30 22 31 24 t28 32 33 34 35 36 37 38 42 46 47 m1 s1Key XYXASLYZTKBYQJ OAUMSBLFSA N1 InChI 1 C47H68O17 c1 10 11 12 13 14 15 39 51 62 42 31 24 41 53 58 9 23 34 25 37 28 2 48 61 43 54 36 50 17 16 33 26 38 59 29 3 49 45 6 7 46 55 63 33 27 35 21 30 22 40 52 57 8 20 32 60 35 18 19 44 4 5 47 42 56 64 34 h12 15 18 19 22 24 28 32 38 42 48 50 55 56H 10 11 16 17 20 21 23 25 27H2 1 9H3 b13 12 15 14 19 18 30 22 31 24 t28 32 33 34 35 36 37 38 42 46 47 m1 s1Key XYXASLYZTKBYQJ OAUMSBLFBY SMILES 1 CCC C C C C C O O C H 1 C C C O OC C C H 2C C H OC O C H CC C H 3C C H C C O3 C C H 4C C C C O OC C C H O4 C C C C 1 O2 O C C O C C OC O C O C H C O Properties Chemical formula C 47H 68O 17 Molar mass 905 044 g mol 1 Except where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa Infobox references Contents 1 Biological effects 2 Chemistry 3 Biosynthesis 4 References 5 Further reading 6 External linksBiological effects editBryostatin 1 is a potent modulator of protein kinase C PKC 2 It showed activity in laboratory tests in cells and model animals so it was brought into clinical trials As of 2014 over thirty clinical trials had been conducted using bryostatin alone and in combination with other agents in both solid tumors and blood tumors it did not show a good enough risk benefit ratio to be advanced further 3 It showed enough promise in animal models of Alzheimer s disease that a Phase II trial was started by 2010 4 the trial was sponsored by the Blanchette Rockefeller Neurosciences Institute 5 Scientists from that institute started a company called Neurotrope 6 and launched another clinical trial in Alzheimer s disease 7 preliminary results of which were released in 2017 8 9 Bryostatin has also been studied in people with HIV 2 Chemistry editBryostatin 1 was first isolated in the 1960s by George Pettit from extracts of a species of bryozoan Bugula neritina based on research from samples originally provided by Jack Rudloe to Jonathan L Hartwell s anticancer drug discovery group at the National Cancer Institute NCI 1 The structure of bryostatin 1 was determined in 1982 10 As of 2010 20 different bryostatins had been isolated 11 The low concentration in bryozoans to extract one gram of bryostatin roughly one tonne of the raw bryozoans is needed makes extraction unviable for large scale production Due to the structural complexity total synthesis has proved difficult with only a few total syntheses reported so far Total syntheses have been published for bryostatins 1 2 3 7 9 and 16 12 13 14 15 16 17 18 19 Among them Wender s total synthesis of bryostatin 1 19 is the shortest synthesis of any bryostatin reported to date A number of structurally simpler synthetic analogs also have been prepared which exhibit similar biological profile and in some cases greater potency which may provide a practical supply for clinical use 20 Biosynthesis edit nbsp B Neritina biosynthetic pathway for bryostatins In B Neritina bryostatin biosynthesis is carried out through a type I polyketide synthase cluster bry BryR is the secondary metabolism homolog of HMG CoA synthase which is the PKS in bacterial primary metabolism In the bryostatin pathway the BryR module catalyzes b Branching between a local acetoacetyl acceptor acyl carrier protein ACP a and an appropriate donor BryU acetyl ACP ACP d 21 The first step involves the loading of a malonyl unit onto a discrete BryU ACP d within an initial BryA module The extended BryU product in BryA is then loaded onto a cysteine sidechain of BryR for interaction with ACP a Upon interaction BryR then catalyzes b Branching facilitating an aldol reaction between the alpha carbon of the BryU unit and the b ketone of ACP a yielding a product similar to HMGS products in primary metabolism After b Branching subsequent dehydration by a BryT enoyl CoA hydratase homolog ECH as well as BryA O methylation and BryB double bond isomerization of the generated HMGS product are carried out in specific domains of the bry cluster These post b Branching steps generate the vinyl methylester moieties which are found in all natural product bryostatins Finally BryC and BryD are responsible for further extension pyran ring closure and cyclization of the HMGS product to produce the novel bryostatin product 22 In the presence of BryR ACP d conversion to holo ACP d was observed prior to b Branching BryR was shown to have high specificity for ACP d only after this conversion Specificity for these protein bound groups is a feature that differentiates the HMGS homologs found in primary metabolism where HMGS typically acts on substrates linked to Coenzyme A from those found in non ribosomal peptide synthase NRPS or PKS pathways such as the bryostatin pathway 21 References edit a b Halford B 24 October 2011 The Bryostatins Tale Chemical and Engineering News 89 43 10 17 doi 10 1021 cen v089n043 p010 a b Kollar P Rajchard J Balounova Z Pazourek J February 2014 Marine natural products bryostatins in preclinical and clinical studies Pharmaceutical Biology 52 2 237 42 doi 10 3109 13880209 2013 804100 PMID 24033119 name Kollar2014rev gt Kollar P Rajchard J Balounova Z Pazourek J February 2014 Marine natural products bryostatins in preclinical and clinical studies Pharmaceutical Biology 52 2 237 42 doi 10 3109 13880209 2013 804100 PMID 24033119 Trindade Silva AE Lim Fong GE Sharp KH Haygood MG December 2010 Bryostatins biological context and biotechnological prospects Current Opinion in Biotechnology 21 6 834 42 doi 10 1016 j copbio 2010 09 018 PMC 4497553 PMID 20971628 Clinical trial number NCT00606164 for Safety Efficacy Pharmacokinetics and Pharmacodynamics Study of Bryostatin 1 in Patients With Alzheimer s Disease at ClinicalTrials gov Alzheimer s Researchers Discover Bryostatin Can Slow Reverse Disease Progression Alzheimer s News Today 19 August 2014 Clinical trial number NCT02431468 for A Study Assessing Bryostatin in the Treatment of Moderately Severe to Severe Alzheimer s Disease at ClinicalTrials gov Taylor NP May 1 2017 Neurotrope misses primary endpoint in Alzheimer s trial FierceBiotech Nelson TJ Sun MK Lim C Sen A Khan T Chirila FV Alkon DL 2017 Bryostatin Effects on Cognitive Function and PKCɛ in Alzheimer s Disease Phase IIa and Expanded Access Trials Journal of Alzheimer s Disease 58 2 521 535 doi 10 3233 JAD 170161 PMC 5438479 PMID 28482641 Pettit GR Cherry Herald L Doubek DL Herald DL Arnold E Clardy J 1982 Isolation and structure of bryostatin 1 J Am Chem Soc 104 24 6846 6848 doi 10 1021 ja00388a092 Hale KJ Manaviazar S April 2010 New approaches to the total synthesis of the bryostatin antitumor macrolides Chemistry An Asian Journal 5 4 704 54 doi 10 1002 asia 200900634 PMID 20354984 Keck GE Poudel YB Cummins TJ Rudra A Covel JA February 2011 Total synthesis of bryostatin 1 Journal of the American Chemical Society 133 4 744 7 doi 10 1021 ja110198y PMC 3030632 PMID 21175177 Evans DA Carter PH Carreira EM Charette AB Prunet JA Lautens M 1999 Total Synthesis of Bryostatin 2 J Am Chem Soc 121 33 7540 7552 doi 10 1021 ja990860j Ohmori K Ogawa Y Obitsu T Ishikawa Y Nishiyama S Yamamura S July 2000 Total Synthesis of Bryostatin Angewandte Chemie 39 13 2290 2294 doi 10 1002 1521 3773 20000703 39 13 lt 2290 AID ANIE2290 gt 3 0 CO 2 6 PMID 10941067 Kageyama M Tamura T Nantz MH Roberts JC Somfai P Whritenour DC Masamune S 1990 Synthesis of Bryostatin 7 J Am Chem Soc 112 20 7407 7408 doi 10 1021 ja00176a058 Lu Y Woo SK Krische MJ September 2011 Total synthesis of bryostatin 7 via C C bond forming hydrogenation Journal of the American Chemical Society 133 35 13876 9 doi 10 1021 ja205673e PMC 3164899 PMID 21780806 Wender PA Schrier AJ June 2011 Total synthesis of bryostatin 9 Journal of the American Chemical Society 133 24 9228 31 doi 10 1021 ja203034k PMC 3129979 PMID 21618969 Trost BM Dong G November 2008 Total synthesis of bryostatin 16 using atom economical and chemoselective approaches Nature 456 7221 485 8 Bibcode 2008Natur 456 485T doi 10 1038 nature07543 PMC 2728752 PMID 19037312 a b Wender PA Hardman CT Ho S Jeffreys MS Maclaren JK Quiroz RV Ryckbosch SM Shimizu AJ Sloane JL Stevens MC October 2017 Scalable synthesis of bryostatin 1 and analogs adjuvant leads against latent HIV Science 358 6360 218 223 Bibcode 2017Sci 358 218W doi 10 1126 science aan7969 PMC 5714505 PMID 29026042 Wender PA Baryza JL Bennett CE Bi FC Brenner SE Clarke MO Horan JC Kan C Lacote E Lippa B Nell PG Turner TM November 2002 The practical synthesis of a novel and highly potent analogue of bryostatin Journal of the American Chemical Society 124 46 13648 9 doi 10 1021 ja027509 PMID 12431074 a b Buchholz TJ Rath CM Lopanik NB Gardner NP Hakansson K Sherman DH October 2010 Polyketide b branching in bryostatin biosynthesis identification of surrogate acetyl ACP donors for BryR an HMG ACP synthase Chemistry amp Biology 17 10 1092 100 doi 10 1016 j chembiol 2010 08 008 PMC 2990979 PMID 21035732 Slocum ST Lowell AN Tripathi AN Shende VV Smith JL Sherman DH 2018 Chemoenzymatic Dissection of Polyketide b Branching in the Bryostatin Pathway Marine Enzymes and Specialized Metabolism Part A Methods in Enzymology Vol 604 pp 207 236 doi 10 1016 bs mie 2018 01 034 ISBN 9780128139592 PMC 6327954 PMID 29779653 Further reading editProksch P Edrada RA Ebel R July 2002 Drugs from the seas current status and microbiological implications Applied Microbiology and Biotechnology 59 2 3 125 34 doi 10 1007 s00253 002 1006 8 PMID 12111137 S2CID 29833324 External links editKilham C The Importance of Drugs From the Sea Fox News Health Archived from the original on 25 April 2012 Bryostatin 1 Aphios Corporation Archived from the original on 2013 12 20 Retrieved 2013 12 19 Bryostatin 2 Aphios Corporation Archived from the original on 2012 11 12 Retrieved 2013 12 19 Bryostatin 3 Aphios Corporation Archived from the original on 2013 12 20 Retrieved 2013 12 19 Retrieved from https en wikipedia org w index php title Bryostatin amp oldid 1205976001, wikipedia, wiki, book, books, library,

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