Structural chemistry of natural and synthetic inoophores and their complexes with cations

Hilgenfeld, Rolf; Saenger, Wolfram

doi:10.1007/3-540-11103-4_6

Cited by 128 publications

(61 citation statements)

References 296 publications

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“…4C). Its torsion angles about the C-O bonds are in the antiperiplanar range and those about the C-C bonds are in the synclinal range, as is common for polyethers 12 . The majority of its interactions with peptide copies C and C* consist of water-mediated hydrogen bonds (Fig.…”

Section: Resultsmentioning

confidence: 87%

Lybatides from Lycium barbarum Contain An Unusual Cystine-stapled Helical Peptide Scaffold

Tan

Wong

Lei

et al. 2017

Sci Rep

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1Cysteine-rich peptides (CRPs) of 2-6 kDa are generally thermally and proteolytically stable because of their multiple cross-bracing disulfide bonds. Here, we report the discovery and characterization of two novel cystine-stapled CRPs, designated lybatide 1 and 2 (lyba1 and lyba2), from the cortex of Lycium barbarum root. Lybatides, 32 to 33 amino acids in length, are hyperstable and display a novel disulfide connectivity with a cysteine motif of C-C-C-C-CC-CC which contains two pairs of adjacent cysteines (-CC-CC). X-ray structure analysis revealed the presence of a single cystine-stabilized (α + π)-helix in lyba2, a rare feature of CRPs. Together, our results suggest that lybatides, one of the smallest four-disulfideconstrained plant CRPs, is a new family of CRPs. Additionally, this study provides new insights into the molecular diversity of plant cysteine-rich peptides and the unusual lybatide scaffold could be developed as a useful template for peptide engineering and therapeutic development.Lycium barbarum, belonging to the Solanaceae family, is a deciduous shrub native to southeastern China 1 . It is the plant that produces the popular herb wolfberries or goji berries. However, the cortex of L. barbarum root ( or DiGuPi in Chinese) is also commonly used as a traditional Chinese medicine for treating chronic low-grade fever, cough, hemoptysis and hematuria, diabetes mellitus and hypertension 1 . A diverse group of secondary metabolites has been isolated from the cortex of L. barbarum root, including alkaloids, flavonoids and flavone glycosides. In addition, small cyclic peptides, namely licyumins A-D, with molecular weights <1 kDa, have been shown to inhibit renin and angiotensin-converting enzymes 2 . However, no bioactive peptides >2 kDa have been reported.Bioactive compounds from medicinal plants have been a source of inspiring structures for drug discovery. A majority of studies focuses on small molecules and secondary metabolites, with few studies focusing on peptides 3,4 . Even in studies relating to identifying peptides from plants, the focus is largely on small cyclic peptides. This bias is attributed to a general perception that peptides >2 kDa are unstable and readily denatured during a decoction preparation or in the gastrointestinal tract after ingestion. This is generally true for large peptides and proteins with molecular weight >8 kDa. However, cysteine-rich peptides (CRPs) with a molecular range of 2-6 kDa and 3-5 disulfide bonds are tolerant to thermal, chemical and proteolytic degradation 5 . As a group, CRPs in this defined chemical space have great potential as a source of leads and inspiration for developing useful drugs from medicinal plants 6,7 . Structurally, plant CRPs within the chemical space of 2-6 kDa can be arbitrarily classified into two major groups (Fig. 1). They are the cystine-stabilized α-helical (CSα) peptides and cystine-stabilized β-peptides. The CSα peptides can be found in plant CRPs >40 residues such as plant defensins and plant thionins. Cystine-stabilized β-peptid...

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Section: Resultsmentioning

confidence: 87%

Lybatides from Lycium barbarum Contain An Unusual Cystine-stapled Helical Peptide Scaffold

Tan

Wong

Lei

et al. 2017

Sci Rep

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“…Monensin is an antibiotic with high selectivity for sodium over other metal cations while valinomycin shows a high selectivity for potassium (Hilgenfeld and Saenger, 1982). The inhibitor DCCD reacts with the carboxyl group of the conserved amino acid residue in the c -subunit present in all ATP synthases to inactivate the enzyme (Shoshan and Selman, 1980; Yoshida et al, 1981).…”

Section: Resultsmentioning

confidence: 99%

Glucose Uptake in Prochlorococcus: Diversity of Kinetics and Effects on the Metabolism

et al. 2017

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We have previously shown that Prochlorococcus sp. SS120 strain takes up glucose by using a multiphasic transporter encoded by the Pro1404 gene. Here, we studied the glucose uptake kinetics in multiple Prochlorococcus strains from different ecotypes, observing diverse values for the Ks constants (15–126.60 nM) and the uptake rates (0.48–6.36 pmol min-1 mg prot-1). Multiphasic kinetics was observed in all studied strains, except for TAK9803-2. Pro1404 gene expression studies during the 21st Atlantic Meridional Transect cruise showed positive correlation with glucose concentrations in the ocean. This suggests that the Pro1404 transporter has been subjected to diversification along the Prochlorococcus evolution, in a process probably driven by the glucose availabilities at the different niches it inhabits. The glucose uptake mechanism seems to be a primary transporter. Glucose addition induced detectable transcriptomic and proteomic changes in Prochlorococcus SS120, but photosynthetic efficiency was unaffected. Our studies indicate that glucose is actively taken up by Prochlorococcus, but its uptake does not significantly alter the trophic ways of this cyanobacterium, which continues performing photosynthesis. Therefore Prochlorococcus seems to remain acting as a fundamentally phototrophic organism, capable of using glucose as an extra resource of carbon and energy when available in the environment.

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“…Fusarium fungi also produce less well-described mycotoxins, so-called emerging mycotoxins, including BEA, ENNs and MON, which have not been included in recommendations by the European legislation. ENNs and BEA are cyclic hexadepsipeptides and can be differentiated according to their alternating N-methylated amino acids (ENN A = isoleucine, ENN B = valine, ENN C = leucin, BEA = phenylalanine), while the core structure is based on an 18-membered ring structure joined by amide and ester bonds (Hilgenfeld and Saenger 1982). Interestingly, ENNs are thought to be rarely produced by trichothecene-producing Fusarium strains (Desjardins 2006).…”

Section: Importance Of Mycotoxins and Their Occurrence In Cereals Andmentioning

confidence: 99%

“…Less extensive reports have been accumulated on the toxicity of the emerging mycotoxins ENN and BEA. At a cellular level, they are able to interact with cations and function as ionophores (Ovchinnikov et al 1974;Hilgenfeld and Saenger 1982). Furthermore, ENNs can lead to lysosomal disruption (Ivanova et al 2012), cell cycle arrest (Gammelsrud et al 2012;Devreese et al 2013), decreased functioning of macrophages (Ficheux et al 2013) and interference with mitochondrial functions (Tonshin et al 2010).…”

Section: Toxicity In Humans and Higher Vertebratesmentioning

confidence: 99%

Risk assessment for mycotoxin contamination in fish feeds in Europe

Pietsch

2019

Mycotoxin Res

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Mycotoxins are difficult to monitor continuously, and a tool to assess the risk would help to judge if there is a particular risk due to the inclusion of certain feed ingredients. For this, the toxin contents of 97 commercial fish feeds have been estimated, and the most prominent toxins in fish feed are calculated to be deoxynivalenol, zearalenone, fumonisins and enniatins. These pose a risk to fish well-being, as can be calculated by the Bayesian models for determining the critical concentrations 5% (CC5) for the different toxins. Besides fishmeal, wheat, soybean products and corn are regularly used as fish feed ingredients. The calculated scenarios show that fish are at high risk of toxin contamination if feed ingredients of low quality are chosen for feed production. Due to this, specific maximum allowable levels for several mycotoxins in fish feeds should be established.

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Structural chemistry of natural and synthetic inoophores and their complexes with cations

Cited by 128 publications

References 296 publications

Lybatides from Lycium barbarum Contain An Unusual Cystine-stapled Helical Peptide Scaffold

Lybatides from Lycium barbarum Contain An Unusual Cystine-stapled Helical Peptide Scaffold

Glucose Uptake in Prochlorococcus: Diversity of Kinetics and Effects on the Metabolism

Risk assessment for mycotoxin contamination in fish feeds in Europe

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