Grassypeptolides F and G, Cyanobacterial Peptides from <i>Lyngbya majuscula</i>

Popplewell, Wendy L.; Ratnayake, Ranjala; Wilson, Jennifer A.; Beutler, John A.; Colburn, Nancy H.; Henrich, Curtis J.; McMahon, James B.; McKee, Tawnya C.

doi:10.1021/np2005083

Cited by 25 publications

(20 citation statements)

References 16 publications

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“…The synthesis of fragment 13 started from the condensation of N-Cbz-N-methyl-l-valine (16) with l-proline tertbutyl ester (17) to give rise to dipeptide 18 in 84 % yield (Scheme 2). Hydrogenolytical removal of the Cbz protecting group in 18 followed by coupling with hydroxy acid 19 [19] by using BOPCl [20] in the presence of triethylamine afforded the corresponding tripeptide, which was deacetylated to furnish 13 in 95 % yield.…”

Section: Resultsmentioning

confidence: 99%

“…Grassypeptolide C is the epimer of 1 at C28, with a l-Phe unit flanking the bis(thiazoline) moiety. Grassypeptolides F (7) and G (8) [17] were isolated from an extract of the Palauan cyanobacterium Lyngbya majuscula by the McKee group in 2011. [14] Grassypeptolides D (5) and E (6), [16] which have identical methyl-substituted thiazoline subunits, were isolated from the marine cyanobacterium Leptolyngbya sp.…”

Section: Introductionmentioning

confidence: 99%

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Total Synthesis and Biological Evaluation of Grassypeptolide A

Liu

Wang

et al. 2013

Chemistry A European J

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Herein, we describe in full our investigations into the synthesis of grassypeptolide A (1) in 17 linear steps with an overall yield of 11.3 %. In particular, this work features the late-stage introduction of sensitive bis(thiazoline) heterocycles and 31-membered macrocyclization conducted at the sterically congested secondary amide site in superb conversion (72 % yield). Biological evaluation indicated that grassypeptolide A significantly inhibited cancer cell proliferation in a dose-dependent manner. It induced cancer cell apoptosis, which was associated with increased cleavage of poly(ADP-ribose) polymerase (PARP) and decreased expression of bcl-2 and bcl-xL. Furthermore, grassypeptolide A also caused cell cycle redistribution by increasing cells in the G1 phase and decreasing cells in the S and G2 phases. In addition, cell cycle arrest was correlated with downregulation of cyclin D and upregulation of p27 and p21.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Total Synthesis and Biological Evaluation of Grassypeptolide A

Liu

Wang

et al. 2013

Chemistry A European J

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“…Bis-thiazoline-containing cyclic depsipeptides Grassypeptolides F (160) and G (161) (Figure S12 ) which contains rare β-amino acid, extensive N-methylation and a large number of d-amino acids was isolated from an extract of Palauan cyanobacterium L. majuscule . Both (160) and (161) were found to have moderate inhibitory activity against the transcription factor AP-1 (IC 50 = 5.2 and 6.0 μM, respectively) (Popplewell et al, 2011 ). An examination of an organic extract of the cyanobacterium Symploca cf.…”

Section: Nrps With Anticancer Potentialmentioning

confidence: 99%

Nonribosomal Peptides from Marine Microbes and Their Antimicrobial and Anticancer Potential

et al. 2017

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Marine environments are largely unexplored and can be a source of new molecules for the treatment of many diseases such as malaria, cancer, tuberculosis, HIV etc. The Marine environment is one of the untapped bioresource of getting pharmacologically active nonribosomal peptides (NRPs). Bioprospecting of marine microbes have achieved many remarkable milestones in pharmaceutics. Till date, more than 50% of drugs which are in clinical use belong to the nonribosomal peptide or mixed polyketide-nonribosomal peptide families of natural products isolated from marine bacteria, cyanobacteria and fungi. In recent years large numbers of nonribosomal have been discovered from marine microbes using multi-disciplinary approaches. The present review covers the NRPs discovered from marine microbes and their pharmacological potential along with role of genomics, proteomics and bioinformatics in discovery and development of nonribosomal peptides drugs.

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“…Synthetic material was used to demonstrate that 1 downregulates cyclin D and upregulates p27 and p21 to modulate cell cycle distribution, and that the compound increases PARP cleavage and decreases BCL‐2 and BCL‐xL expression, correlating with the proapoptotic activity of 1 12. Additional grassypeptolides were discovered by other groups;13, 14 all show some degree of toxicity, and analogues with 28 S configuration, such as 3 , show the greatest potency.…”

Section: Ic50 Values Of Grassypeptolides Against Cathepsin L Dipeptimentioning

confidence: 99%

Grassypeptolides as Natural Inhibitors of Dipeptidyl Peptidase 8 and T‐Cell Activation

et al. 2014

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Natural products made by marine cyanobacteria are often highly modified peptides and depsipeptides that have the potential to act as inhibitors for proteases. In the interest of finding novel protease inhibition activity and selectivity grassypeptolide A (1) was screened against a panel of proteases and found to selectively inhibit DPP8 over DPP4. Grassypeptolides were also found to inhibit IL-2 production and proliferation in activated T-cells, consistent with a putative role of DPP8 in the immune system. These effects were also observed in Jurkat cells, and DPP activity in Jurkat cell cytosol was shown to be inhibited by grassypeptolides. In silico docking suggests two possible binding modes of grassypeptolides – both at the active site of DPP8 and at one of the entrances to the internal cavity. Collectively these results suggest that grassypeptolides may be useful tool compounds in the study of DPP8 function.

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Grassypeptolides F and G, Cyanobacterial Peptides from Lyngbya majuscula

Cited by 25 publications

References 16 publications

Total Synthesis and Biological Evaluation of Grassypeptolide A

Total Synthesis and Biological Evaluation of Grassypeptolide A

Nonribosomal Peptides from Marine Microbes and Their Antimicrobial and Anticancer Potential

Grassypeptolides as Natural Inhibitors of Dipeptidyl Peptidase 8 and T‐Cell Activation

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