406938-53-2Relevant academic research and scientific papers
Zelkovamycins B-E, Cyclic Octapeptides Containing Rare Amino Acid Residues from an Endophytic Kitasatospora sp
Cen, Shan,Connolly, Jack A.,Gan, Maoluo,Goss, Rebecca J. M.,Hao, Xiaomeng,Liu, Yufeng,Wang, Yujia,Yu, Jiaqing,Yu, Liyan,Zhang, Yuqin
, p. 9346 - 9350 (2020/12/21)
Four unusual cyclopeptides, zelkovamycins B-E (1-4), were isolated from an endophytic Kitasatospora sp. Zelkovamycin B was featured by an unprecedented 3-methyl-5-hydroxypyrrolidine-2,4-dione ring system linked to the cyclopeptide skeleton. Their structures and full configurations were established by spectroscopic analysis, Marfey's method, and NMR calculations. A plausible biosynthetic pathway for zelkovamycins was proposed based on gene cluster analysis. Zelkovamycin E displayed potent inhibitory activity against H1N1 influenza A virus.
De novo Biosynthesis of “Non-Natural” Thaxtomin Phytotoxins
Winn, Michael,Francis, Daniel,Micklefield, Jason
supporting information, p. 6830 - 6833 (2018/06/04)
Thaxtomins are diketopiperazine phytotoxins produced by Streptomyces scabies and other actinobacterial plant pathogens that inhibit cellulose biosynthesis in plants. Due to their potent bioactivity and novel mode of action there has been considerable interest in developing thaxtomins as herbicides for crop protection. To address the need for more stable derivatives, we have developed a new approach for structural diversification of thaxtomins. Genes encoding the thaxtomin NRPS from S. scabies, along with genes encoding a promiscuous tryptophan synthase (TrpS) from Salmonella typhimurium, were assembled in a heterologous host Streptomyces albus. Upon feeding indole derivatives to the engineered S. albus strain, tryptophan intermediates with alternative substituents are biosynthesized and incorporated by the NRPS to deliver a series of thaxtomins with different functionalities in place of the nitro group. The approach described herein, demonstrates how genes from different pathways and different bacterial origins can be combined in a heterologous host to create a de novo biosynthetic pathway to “non-natural” product target compounds.
Multisite prenylation of 4-substituted tryptophans by dimethylallyltryptophan synthase
Rudolf, Jeffrey D.,Wang, Hong,Poulter, C. Dale
, p. 1895 - 1902 (2013/04/23)
The aromatic prenyltransferase dimethylallyltryptophan synthase in Claviceps purpurea catalyzes the normal prenylation of tryptophan at C4 of the indole nucleus in the first committed step of ergot alkaloid biosynthesis. 4-Methyltryptophan is a competitive inhibitor of the enzyme that has been used in kinetic studies. Upon investigation of background activity during incubations of 4-methyltryptophan with dimethylallyl diphosphate, we found that the analogue was an alternate substrate, which gave four products. The structures of three of these compounds were established by 1H NMR and 2D NMR studies and revealed that dimethylallyltryptophan synthase catalyzed both normal and reverse prenylation at C3 of the indole ring and normal prenylation of N1. Similarly, 4-methoxytryptophan was an alternate substrate, giving normal prenylation at C5 as the major product. 4-Aminotryptophan, another alternate substrate, gave normal prenylation at C5 and C7. The ability of dimethylallyltryptophan synthase to prenylate at five different sites on the indole nucleus, with normal and reverse prenylation at one of the sites, is consistent with a dissociative electrophilic alkylation of the indole ring, where orientation of the substrates within the active site and substituent electronic effects determine the position and type of prenylation. These results suggest a common mechanism for prenylation of tryptophan by all of the members of the structurally related dimethylallyltryptophan synthase family.
IMPROVED METHOD FOR PRODUCING INTERMEDIATES FOR THE PRODUCTION OF MACROCYCLES THAT ARE INHIBITORS OF THE PROTEASOMIC DEGRADATION OF P27, SUCH AS ARGYRIN AND DERIVATIVES THEREOF
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Page/Page column 11-12, (2011/07/07)
The present invention relates to an improved method for the synthesis of particular macrocycles that are inhibitors of the proteasomic degradation of p27, in particular argyrin and derivatives thereof.
Method for producing intermediates for the production of novel macrocycles that are inhibitors of the proteasomic degradation of p27, such as argyrin and derivatives thereof, and uses of said macrocycles
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, (2010/01/07)
The present invention relates to the use of particular macrocycles that are inhibitors of the proteasomic degradation of p27, in particular argyrin and derivatives thereof, for a treatment in a variety of conditions, such as the induction of immunotolerance, autoimmune diseases, bacterial infections, and proliferative diseases, such as cancers.
Total synthesis of the cyclic peptide Argyrin B
Ley, Steven V.,Priour, Alain
, p. 3995 - 4004 (2007/10/03)
The details of the total synthesis of Argyrin B, a natural product with immunosuppressive properties, are reported below. The two most unusual amino acid residues of this cyclic peptide are 4-methoxytryptophan and dehydroalanine, which were obtained by mo
Total synthesis of the cyclic heptapeptide Argyrin B: A new potent inhibitor of T-cell independent antibody formation
Ley, Steven V.,Prieur, Alain,Heusser, Christoph
, p. 711 - 714 (2007/10/03)
(equation presented) Argyrin B (1) The total synthesis of Argyrin B (1) is presented using a synthetic plan that is convergent and flexible and conserves the stereogenic centers. The unusual amino acid 4-methoxy tryptophan (6) was obtained via an enzymati
