Membrane properties of hydroxycholesterols related to the brain cholesterol metabolism

• Malte Hilsch,
• Ivan Haralampiev,
• Peter Müller,
• Daniel Huster and
• Holger A. Scheidt

Beilstein J. Org. Chem. 2017, 13, 720–727, doi:10.3762/bjoc.13.71

• influence on lipid chain order, membrane permeability and formation of lateral domains. Keywords: cholesterol; fluorescence; hydroxycholesterol; membrane structure; NMR; Introduction Cholesterol is a major component of mammalian cell membranes with various biological functions. It plays a key role in

• maintaining the membrane’s barrier function by increasing the bilayer packing density through condensing the phospholipids. Furthermore, cholesterol is an important player in the dynamic domain structure of the plasma membrane and the formation of lateral lipid domains with relevance to membrane protein

• of a human being [4][6]. Insoluble cholesterol is transported in the blood in small lipoprotein particles of varying density and the rate, at which cholesterol crosses the lipid membrane, is extremely low [7]. To overcome the blood–brain barrier, nature has developed efficient mechanisms to convert

How and why kinetics, thermodynamics, and chemistry induce the logic of biological evolution

• Addy Pross and
• Robert Pascal

Beilstein J. Org. Chem. 2017, 13, 665–674, doi:10.3762/bjoc.13.66

• pathways, a wide range of precursors similar to those found in biochemistry (amino acids, nucleotides and lipid precursors). Conclusion This paper attempts to place life and its emergence within a general physicochemical context. Once it is appreciated that life emerged from inanimate beginnings in a well

Conjecture and hypothesis: The importance of reality checks

• David Deamer

Beilstein J. Org. Chem. 2017, 13, 620–624, doi:10.3762/bjoc.13.60

• mononucleotides [22][28][29]. Because the resulting polymers can be encapsulated in lipid vesicles, it has been proposed that the resulting protocells are candidates for combinatorial selection and the first steps of evolution [30]. Conclusion From the above discussion, alternative conjectures have been published

Pd- and Cu-catalyzed approaches in the syntheses of new cholane aminoanthraquinone pincer-like ligands

• Nikolay V. Lukashev,
• Gennadii A. Grabovyi,
• Dmitry A. Erzunov,
• Alexey V. Kazantsev,
• Gennadij V. Latyshev,
• Alexei D. Averin and
• Irina P. Beletskaya.

Beilstein J. Org. Chem. 2017, 13, 564–570, doi:10.3762/bjoc.13.55

• transport of anions through lipid membranes [19][20][21][22]. Some of similar pincer compounds can be used as receptors for organic molecules; e.g., polyamino derivatives based on cholane skeleton can form complexes with amino acids [23] and pincer-like conjugates of deoxycholic acid and aminopyrene can

• arylaminocholanes and cholane-diaminoanthraquinone derivatives by Pd- and Cu-catalyzed amination. Such compounds not only have cation binding properties, but also might be easily introduced in lipid membranes to form ion channels. Appropriate close location of lipophilic steroid fragments in bis(cholanediamino

Synthesis and evaluation of anti-oxidant and cytotoxic activities of novel 10-undecenoic acid methyl ester based lipoconjugates of phenolic acids

• Naganna Narra,
• Shiva Shanker Kaki,
• Rachapudi Badari Narayana Prasad,
• Sunil Misra,
• Koude Dhevendar,
• Venkateshwarlu Kontham and
• Padmaja V. Korlipara

Beilstein J. Org. Chem. 2017, 13, 26–32, doi:10.3762/bjoc.13.4

• Naganna Narra Shiva Shanker Kaki Rachapudi Badari Narayana Prasad Sunil Misra Koude Dhevendar Venkateshwarlu Kontham Padmaja V. Korlipara Centre for Lipid Research, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, India Academy of Scientific and Innovative Research, New

• phenolics and the lipid involved in one chemical entity [4][5]. Lipids, especially fatty acids and their derivatives are known for their broad spectrum of activity which expands their application in developing new hybrid biomolecules which help in host defenses against potential pathogenic microbes

• compounds could be useful as potential novel lipid derivatives because of the presence of lipophilic chain and the phenolic amide conjugate. Results and Discussion Synthesis 10-Undecenoic acid was chosen as the lipid part as the derivatives of undecenoic acid have been reported to be potent bioactive

Synthesis of multi-lactose-appended β-cyclodextrin and its cholesterol-lowering effects in Niemann–Pick type C disease-like HepG2 cells

• Keiichi Motoyama,
• Rena Nishiyama,
• Yuki Maeda,
• Taishi Higashi,
• Yoichi Ishitsuka,
• Yuki Kondo,
• Tetsumi Irie,
• Takumi Era and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2017, 13, 10–18, doi:10.3762/bjoc.13.2

• NPC-like HepG2 cells via asialoglycoprotein receptor (ASGPR)-mediated endocytosis. Keywords: asialoglycoprotein receptor; cholesterol; cyclodextrin; lactose; Niemann–Pick type C disease; Introduction The Niemann–Pick type C (NPC) disease is a lipid storage disorder with the accumulation of membrane

Biochemical and structural characterisation of the second oxidative crosslinking step during the biosynthesis of the glycopeptide antibiotic A47934

• Veronika Ulrich,
• Clara Brieke and
• Max J. Cryle

Beilstein J. Org. Chem. 2016, 12, 2849–2864, doi:10.3762/bjoc.12.284

• enables them to bind to the dipeptide terminus of the peptidoglycan precursor lipid II [1][2]. This three-dimensional structure is generated by the high degree of crosslinking exhibited by the glycopeptide antibiotics: in the case of the two most widely known natural examples (vancomycin and teicoplanin

Benzothiadiazole oligoene fatty acids: fluorescent dyes with large Stokes shifts

• Lukas J. Patalag and
• Daniel B. Werz

Beilstein J. Org. Chem. 2016, 12, 2739–2747, doi:10.3762/bjoc.12.270

• isomerization are presented. The absorption properties are modulated by the number of conjugated C=C double bonds of the oligoene chain ranging from one to three. Large Stokes shifts of about 4900–5700 cm−1 and fluorescence quantum yields of up to 0.44 were observed. Keywords: fatty acid; fluorescence; lipid

• sufficient to understand membrane dynamics and function. Often membrane domains are formed in which certain lipids, glycolipids or proteins are enriched [2][3][4]. Such domains – also called lipid rafts – do not only differ in their chemical composition, but also show different physical properties (e.g

• ., differences in membrane thickness and stiffness, different diffusion coefficients etc.) [5][6]. Tools to investigate lipid membranes are multifaceted; however, all optical methods are hampered by the missing absorption and fluorescence properties of natural occurring lipid components. Therefore, indirect

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• involving CDs has revolved around their ability to manipulate lipid (phospholipids and cholesterol) composition in different cells [55][56][57][58]. Although numerous studies deal of this topic, the mechanism of this process is poorly investigated (i.e., only the consequences of this phenomenon are reported

• and cholesterol, respectively, whereas γ-CD is generally less lipid-selective. In more detail, the CD affinity for solubilizing various lipid components of the erythrocyte membranes are in the order γ-CD << β-CD < α-CD for phospholipids and α-CD < γ-CD << β-CD for cholesterol [58]. These findings are

• activity in comparison with the parent CDs while the lipophilic ones (e.g., methylated CDs) demonstrate the strongest hemolytic activities [62]. As for parent CDs, these differences are ascribed to the different solubilization effects of lipid components and their sequestration in the external aqueous

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• using traditional techniques. Teixobactin (17) exhibits bactericidal activity through binding of Lipid II, a precursor of peptidoglycan, and therefore shows great potential as the foundation for discovery of a new generation of antibiotics to overcome the development of antimicrobial resistance

• which involves binding to Lipid II, inhibiting one of the membrane-associated steps of peptidoglycan biosynthesis [43][44]. Analogues of teixobactin (17) have undergone biological testing and results show that the L-allo-enduracididine (3, blue, Figure 7) residue is important for potent antibacterial

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

Biradical vs singlet oxygen photogeneration in suprofen–cholesterol systems

• Fabrizio Palumbo,
• Francisco Bosca,
• Isabel M. Morera,
• Inmaculada Andreu and
• Miguel A. Miranda

Beilstein J. Org. Chem. 2016, 12, 1196–1202, doi:10.3762/bjoc.12.115

• singlet oxygen, thus being able to initiate Ch oxidation from their triplet excited states following either of the two competing mechanistic pathways. Keywords: aryl ketones; hydrogen abstraction; lipid peroxidation; photoproducts; triplet excited state; Introduction Among the constituents of cell

• membranes, cholesterol (Ch) is the most important lipidic building block. It is required for permeability, fluidity, and integrity of all animal cell membranes. However, as an unsaturated lipid, Ch is susceptible to oxidative degradation, which can result in potentially pathologic consequences encompassing

Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines

• Eric Buchy,
• Branko Vukosavljevic,
• Maike Windbergs,
• Dunja Sobot,
• Camille Dejean,
• Simona Mura,
• Patrick Couvreur and
• Didier Desmaële

Beilstein J. Org. Chem. 2016, 12, 1127–1135, doi:10.3762/bjoc.12.109

• developed covering all aspects of medicine. Among them, lipid drug conjugates (LDC) were especially developed for the delivery of hydrophilic drugs by covalent coupling with lipid components [3][4]. In this context we recently found that the chemical conjugation of squalene, a natural and biocompatible

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• illustrated in Figure 4 and has been described in detail in several reviews (e.g., [51][53][54][55][56][57]). It can be divided into three parts: first, the formation of the monomeric building blocks in the cytosol (Figure 4, step A); second, the membrane-bound steps with the attachment to the lipid linker

• been reported elsewhere [52]. The membrane-associated steps commence with the transfer of UDP-MurNAc-pentapeptide to the lipid carrier undecaprenyl phosphate, catalysed by translocase I (MraY), to give lipid I (Figure 4, product of step B). The glycosyltransferase MurG attaches a GlcNAc sugar to

• furnish lipid II (Figure 4, product of step C). This building block is then transported to the extracellular side of the membrane. It is speculated that there might be some kind of 'flippase' involved but this particular step is still unclear and requires further investigation [55]. On the extracellular

Art, auto-mechanics, and supramolecular chemistry. A merging of hobbies and career

• Eric V. Anslyn

Beilstein J. Org. Chem. 2016, 12, 362–376, doi:10.3762/bjoc.12.40

• Molecular Probes. The directions that Vincent Rotello is taking the field of differential sensing, toward that of biological applications, is one clear future. We are similarly moving to biological applications with kinase and lipid analysis, and cellular classification. But, even beverage analysis, complex

Physical properties and biological activities of hesperetin and naringenin in complex with methylated β-cyclodextrin

• Waratchada Sangpheak,
• Jintawee Kicuntod,
• Roswitha Schuster,
• Thanyada Rungrotmongkol,
• Peter Wolschann,
• Nawee Kungwan,
• Helmut Viernstein,
• Monika Mueller and
• Piamsook Pongsawasdi

Beilstein J. Org. Chem. 2015, 11, 2763–2773, doi:10.3762/bjoc.11.297

• , grapefruit and orange. Several reports on biological effects of hesperetin and naringenin have been found [6], including blood lipid- and cholesterol-lowering effects [7][8][9], anti-inflammatory [10][11][12][13] and anticancer [14][15][16] activities, improved microcirculation, recovery of venous ulcers

A concise and efficient synthesis of benzimidazo[1,2-c]quinazolines through CuI-catalyzed intramolecular N-arylations

• Xinlong Pang,
• Chao Chen,
• Ming Li and
• Chanjuan Xi

Beilstein J. Org. Chem. 2015, 11, 2365–2369, doi:10.3762/bjoc.11.258

• ]quinazolines were intensively investigated and promising biological activities were observed, such as anticancer, antiviral, antimicrobial, anti-inflammatory and anticonvulsant [3][4][5]. Indeed, some of them are already used as antimicrobial agents and lipid peroxidation inhibitors [6]. Consequently, the

Cholesterol lowering effects of mono-lactose-appended β-cyclodextrin in Niemann–Pick type C disease-like HepG2 cells

• Keiichi Motoyama,
• Yumi Hirai,
• Rena Nishiyama,
• Yuki Maeda,
• Taishi Higashi,
• Yoichi Ishitsuka,
• Yuki Kondo,
• Tetsumi Irie,
• Takumi Era and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2015, 11, 2079–2086, doi:10.3762/bjoc.11.224

• effects of CyDs in NPC cells are as follows; 1) CyDs may extract the free form of cholesterol from plasma membranes of lipid rafts, and then cholesterol in endolysosomes are transported to plasma membrane to supply, 2) the endocytosed CyDs may transport cholesterol from endolysosomes, and 3) the

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• able to disrupt the cholesterol-rich lipid envelope and inactivate viral invasion [17]. Cholesterol-based hydrazones exhibited insecticidal activity against the larval stage of Mythimna separate (Walker) [18]. Cholesterol–carbamate conjugates, for instance (3β)-cholest-5-en-3-yl (2-aminoethyl)carbamate

• cell line but it was 2.3 fold less active than doxorubicin in vitro. Therefore, this article describes the synthesis of analogues of VI with different lipid, glycon and chalcone [25][26] tags to assay and evaluate their in vitro antimicrobial and cytotoxic activities against the above mentioned

• were 37–64% less active than ampicillin. Compound 11a, that is modified with a C11 lipid tail, was the least active cholesterol derivative, thus, it was 73% less active than the control. On the other hand, derivatives 6c, 7b and the bicholesterol 13 were the most active cholesterols against S. aureus

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• ethylene (24) under high dilution conditions to deliver the tetracyclic compound 49 in 62% yield (Scheme 7). To assemble 5-F2-isoprostanes, lipid oxidation metabolites, various functionalized cyclobutene derivatives were subjected to a RRM sequence [12]. Cyclobutene derivative 50 in the presence of the

Antioxidant potential of curcumin-related compounds studied by chemiluminescence kinetics, chain-breaking efficiencies, scavenging activity (ORAC) and DFT calculations

• Adriana K. Slavova-Kazakova,
• Silvia E. Angelova,
• Timur L. Veprintsev,
• Petko Denev,
• Davide Fabbri,
• Maria Antonietta Dettori,
• Maria Kratchanova,
• Vladimir V. Naumov,
• Aleksei V. Trofimov,
• Rostislav F. Vasil’ev,
• Giovanna Delogu and
• Vessela D. Kancheva

Beilstein J. Org. Chem. 2015, 11, 1398–1411, doi:10.3762/bjoc.11.151

• reactions of the antioxidants with peroxyl radicals; model 2 – lipid autoxidation (lipidAO) used for assessing the chain-breaking antioxidant efficiency and reactivity; model 3 – oxygen radical absorbance capacity (ORAC), which yields the activity against peroxyl radicals generated by an azoinitiator; model

• were applied: model 1 – chemiluminescence of a hydrocarbon substrate used for determination of the rate constants (kA) of the reactions of the antioxidants with peroxyl radicals (RO2•); model 2 – lipid autoxidation used for assessing the chain-breaking antioxidant efficiency and reactivity; model 3

• the side chain that influences the dihedral angle of biphenyl structure. Model 2: Lipid autoxidation Kinetic curves of the lipid autoxidation at concentrations of 1 mM of the studied compounds and of DL-α-tocopherol (11) are presented in Figure 4 and the main kinetic parameters, characterizing the

Terminal lipophilization of a unique DNA dodecamer by various nucleolipid headgroups: Their incorporation into artificial lipid bilayers and hydrodynamic properties

• Emma Werz and
• Helmut Rosemeyer

Beilstein J. Org. Chem. 2015, 11, 913–929, doi:10.3762/bjoc.11.103

• oligonucleotides (LONs 10–15), each terminally lipophilized with different nucleolipid head groups, were synthesized using the recently prepared phosphoramidites 4b–9b. The insertion of the LONs within an artificial lipid bilayer, composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl

• lipophilicity but mainly the chemical structure and topology of the head group is of decisive importance for the optimal interaction of a lipo-oligonucleotide with an artificial lipid bilayer. Moreover, fluorescence half-live and diffusion time values were measured to determine the diffusion coefficients of the

• lipo-oligonucleotides. Keywords: lipid bilayer; lipo-oligonucleotides; nucleic acids; nucleolipids; Introduction For proper cell function, the biosynthetic lipophilization of proteins and carbohydrates, such as palmitoylation and farnesylation, is of decisive importance [1]. The same seems to be true

Impact of multivalent charge presentation on peptide–nanoparticle aggregation

• Daniel Schöne,
• Boris Schade,
• Christoph Böttcher and
• Beate Koksch

Beilstein J. Org. Chem. 2015, 11, 792–803, doi:10.3762/bjoc.11.89

• of assemblies is most likely achieved by hydrogen bonds or other common receptor–binding interactions [28]. Although it is known that nanoparticles can be organised by binding to membranes by means of electrostatic interactions between the charged head group of the lipid and the oppositely charged

Potential of acylated peptides to target the influenza A virus

• Daniel Lauster,
• Damian Pawolski,
• Julian Storm,
• Kai Ludwig,
• Rudolf Volkmer,
• Henry Memczak,
• Andreas Herrmann and
• Sumati Bhatia

Beilstein J. Org. Chem. 2015, 11, 589–595, doi:10.3762/bjoc.11.65

• those peptides to form large amyloid-like supramolecular assemblies. Second, in vivo, the large excess of cell surface membranes provides an unspecific target for the stearylated peptides. We show that acylated peptides insert into the lipid phase of such membranes. Eventually, our study reveals serious

• concentrations being in the range from 7 to 100 µM. It is important to note that the unspecific interaction of our compounds with cells can reduce the efficiency of compounds to prevent virus binding to cells, possibly even by incorporation into the lipid phase of membranes (see below). In addition to the human

• H5N1 at an MOI of 0.05 48 h post infection. Interaction with lipid membranes Although the above presented data may be promising in terms of efficient inhibition of influenza virus binding and, thus, infection, we have to take into account that the conditions of these experiments do not match the in

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• . L., Rosaceae) and pomegranates (Punica granatum L., Lythraceae). It shows potent antioxidant effects by radical scavenging and the inhibition of lipid peroxidation [28][29]. Ellagic acid is also capable of interfering with some angiogenesis-dependent pathways. It exhibits anticarcinogenic activity