The conventional turns rather than irregular γ-/β-turn secondary structures accounting for the antitumor activities of cyclic peptide Phakellistatin 6 analogs

Zhao, Lishuang; Wu, Jingwan; Bao, Yujun; Jiang, Shitian; Wang, Zhiqiang; Jin, Yingxue; Qu, Fengyu

doi:10.1016/j.tet.2019.130881

Cited by 15 publications

(18 citation statements)

References 46 publications

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“…This may interfere with enzyme activity since HB drifts into DPP4, but eventually binds to the receptor in the conformation with the lowest binding affinity. In a series of research on marine cyclopeptides, it was observed that the rigidity of a proline-rich cyclic structure will reduce the entropy of the Gibbs free energy and enhance the binding force [ 43 , 44 , 45 , 64 ]. According to the observation of HB in DPP4, it was found that proline-rich fragments can provide multiple sites to establish hydrogen bonds in a small area.…”

Section: Resultsmentioning

confidence: 99%

“…Many sponge-derived cyclopeptides such as the “Phakellistatin 1–19” series are well-known cytostatic compounds for the development of anticancer agents. In the “structure–activity relationship” study of Phakellistatins, it was found that because proline residues can reduce the flexibility of the backbone, the proline-rich cyclopeptides can enhance the selectivity and affinity of their receptors [ 43 , 44 , 45 ]. The health-oriented hydrolyzed dairy products also emphasize the role of their proline-rich peptides.…”

Section: Introductionmentioning

confidence: 99%

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The Potential Role of Cyclopeptides from Pseudostellaria heterophylla, Linum usitatissimum and Drymaria diandra, and Peptides Derived from Heterophyllin B as Dipeptidyl Peptidase IV Inhibitors for the Treatment of Type 2 Diabetes: An In Silico Study

Liao

Tzen

2022

Metabolites

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Dipeptidyl peptidase 4 (DPP4) inhibitors can treat type 2 diabetes by slowing GLP-1 degradation to increase insulin secretion. Studies have reported that Pseudostellaria heterophylla, Linum usita-tissimum (flaxseed), and Drymaria diandra, plants rich in Caryophyllaceae-type cyclopeptides and commonly used as herbal or dietary supplements, are effective in controlling blood sugar. The active site of DPP4 is in a cavity large enough to accommodate their cyclopeptides. Molecular modeling by AutoDock Vina reveals that certain cyclopeptides in these plants have the potential for DPP4 inhibition. In particular, “Heterophyllin B” from P. heterophylla, “Cyclolinopeptide C” from flaxseed, and “Diandrine C” from D. diandra, with binding affinities of −10.4, −10.0, and −10.7 kcal/mol, are promising. Docking suggests that DPP4 inhibition may be one of the reasons why these three plants are beneficial for lowering blood sugar. Because many protein hydrolysates have shown the effect of DPP4 inhibition, a series of peptides derived from Heterophyllin B precursor “IFGGLPPP” were included in the study. It was observed that IFWPPP (−10.5 kcal/mol), IFGGWPPP (−11.4 kcal/mol), and IFGWPPP (−12.0 kcal/mol) showed good binding affinity and interaction for DPP4. Various IFGGLPPP derivatives have the potential to serve as scaffolds for the design of novel DPP4 inhibitors.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Potential Role of Cyclopeptides from Pseudostellaria heterophylla, Linum usitatissimum and Drymaria diandra, and Peptides Derived from Heterophyllin B as Dipeptidyl Peptidase IV Inhibitors for the Treatment of Type 2 Diabetes: An In Silico Study

Liao

Tzen

2022

Metabolites

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“…The results showed that the two analogues of phakillestatin 6 had IC 50 values of 11.10 µg/mL (DLD-S) and 7.79 µg/mL (LLD-S) for HepG2. Furthermore, LDH activity assay and electron microscopy confirmed the occurrence of membrane disruption as the possible mechanism of action [ 53 ].…”

Section: Cyclic Peptides For Cancermentioning

confidence: 99%

Cyclic Peptides for the Treatment of Cancers: A Review

et al. 2022

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Cyclic peptides have been widely reported to have therapeutic abilities in the treatment of cancer. This has been proven through in vitro and in vivo studies against breast, lung, liver, colon, and prostate cancers, among others. The multitude of data available in the literature supports the potential of cyclic peptides as anticancer agents. This review summarizes the findings from previously reported studies and discusses the different cyclic peptide compounds, the sources, and their modes of action as anticancer agents. The prospects and future of cyclic peptides will also be described to give an overview on the direction of cyclic peptide development for clinical applications.

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“…Previously we synthesized analogs of the natural cyclopeptide Phakellistatin 6 by the IPETC method and found that they had inhibitory ability against cancer cell proliferation, suggesting that the rigid isoindolinone block played an important role in the cyclic structures. 8 Marine organisms produce a variety of cyclic peptides with unique structures and extensive biological activities, such as antitumor activity, antifungal activity, and immune suppressive activities. 9−11 In some small cyclic peptides derived from marine organisms, a slight change in the amino acid sequence could lead to a very different biological activity, even if the type of amino acid residues was identical.…”

mentioning

confidence: 99%

Novel Isoindolinone-Based Analogs of the Natural Cyclic Peptide Fenestin A: Synthesis and Antitumor Activity

Zhang

Wang

et al. 2022

ACS Med. Chem. Lett.

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Small-and medium-sized cyclopeptides have been found to have extensive bioactivities and have drawn much attention from medicinal chemists. In the work described in this paper, various cyclic peptide analogs of Fenestin A were synthesized by intramolecular photoinduced electron-transfer cyclization reactions to study the influence of slight structural changes on the bioactivity of small cyclopeptides. The incorporation of thiazole and rigid isoindolinone fragments was found to improve the bioactivity of the cyclopeptide. Detailed in vitro studies of the apoptosis mechanism, mitochondrial membrane potential, cell cycle, intracellular Ca 2+ concentration, and lactate dehydrogenase activity following treatment with a cyclopeptide showed that the cyclopeptide could induce apoptosis of tumor cells and lead to cycle arrest in the G2/M phase. The research also suggested that the photoinduced reaction could be applied to construct cyclic peptides stereoselectively, and the introduction of rigid fragments could enhance the biological activity of cyclopeptide drugs.

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The conventional turns rather than irregular γ-/β-turn secondary structures accounting for the antitumor activities of cyclic peptide Phakellistatin 6 analogs

Cited by 15 publications

References 46 publications

The Potential Role of Cyclopeptides from Pseudostellaria heterophylla, Linum usitatissimum and Drymaria diandra, and Peptides Derived from Heterophyllin B as Dipeptidyl Peptidase IV Inhibitors for the Treatment of Type 2 Diabetes: An In Silico Study

The Potential Role of Cyclopeptides from Pseudostellaria heterophylla, Linum usitatissimum and Drymaria diandra, and Peptides Derived from Heterophyllin B as Dipeptidyl Peptidase IV Inhibitors for the Treatment of Type 2 Diabetes: An In Silico Study

Cyclic Peptides for the Treatment of Cancers: A Review

Novel Isoindolinone-Based Analogs of the Natural Cyclic Peptide Fenestin A: Synthesis and Antitumor Activity

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