Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors

• Rebeka Jójárt,
• Szabolcs Pécsy,
• György Keglevich,
• Mihály Szécsi,
• Réka Rigó,
• Csilla Özvegy-Laczka,
• Gábor Kecskeméti and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 2838–2845, doi:10.3762/bjoc.14.262

• position, size and polarity are expected to have remarkable influence on the affinity for the target proteins. Investigation of the influence of the nature of the atom attached directly to the aromatic ring A of 13α-estrone and the stereochemistry of the introduced moiety would also be of high interest

Unprecedented nucleophile-promoted 1,7-S or Se shift reactions under Pummerer reaction conditions of 4-alkenyl-3-sulfinylmethylpyrroles

• Takashi Go,
• Akane Morimatsu,
• Hiroaki Wasada,
• Genzoh Tanabe,
• Osamu Muraoka,
• Yoshiharu Sawada and
• Mitsuhiro Yoshimatsu

Beilstein J. Org. Chem. 2018, 14, 2722–2729, doi:10.3762/bjoc.14.250

• compounds operate by inhibiting proteins or enzymes that regulate cell cycles, including cyclin-dependent kinases [9], tyrosine kinase [10], glycogen-synthase kinase and mitochondrial malate dehydrogenase [11]. These interesting biological activities led us to develop one-pot sequential or cascade protocols

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• complex molecular processes in a cell are discerned by tagging fluorescent probes or radioactive tracers to a targeting ligand that will undergo internalization after binding to cell surface proteins overexpressed in diseased conditions. The internalized tracers along with the targeting ligand act as a

• ]. Therefore, targeting these biomarkers brings forth new insight to know the cause and treatment for such ailments. These biomarkers belong to a family of cell surface transmembrane proteins [22] over-expressed mainly in diseased tissues and exploited in delivering chemical tools for early diagnosis of

• folate receptors. The in vitro uptake study has been performed using laser scanning confocal microscopy and the bioconjugates are found to be delivered specifically to cells expressing corresponding cell surface proteins. The small molecule targeted imaging probes prepared in this study are designed for

Non-native autoinducer analogs capable of modulating the SdiA quorum sensing receptor in Salmonella enterica serovar Typhimurium

• Matthew J. Styles and
• Helen E. Blackwell

Beilstein J. Org. Chem. 2018, 14, 2651–2664, doi:10.3762/bjoc.14.243

• proteins consist of two domains: a larger N-terminal ligand-binding domain (LBD) connected to a smaller C-terminal DNA-binding domain (DBD). In 2006, the structure of the EHEC SdiA LBD was solved by NMR in the presence and absence of AHL and demonstrated increased folding and structure upon ligand binding

• other reported full length LuxR-type proteins (i.e., TraR and QscR) [21][22], albeit with different interdomain interactions that likely direct the final assembly. Despite these reported structures, we still have a very poor understanding of non-native ligand–receptor interactions involved in LuxR-type

• receptor activation (or inactivation). Most LuxR-type proteins are highly unstable in vitro in the absence of an agonist ligand, and this instability is typically heightened in the presence of an antagonist [38]. As such, the observed stability of EHEC SdiA in vitro, both in the absence and presence of

The design and synthesis of an antibacterial phenothiazine–siderophore conjugate

• Abed Tarapdar,
• James K. S. Norris,
• Oliver Sampson,
• Galina Mukamolova and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2018, 14, 2646–2650, doi:10.3762/bjoc.14.242

• antibiotics to the bacterial cell [3]. Iron is essential for bacterial survival and bacteria secrete high affinity iron chelating molecules to scavenge and solubilise Fe3+ from the extracellular environment [3]. The siderophore–Fe complex is recognised by specific receptor proteins on the outer membrane of

• achieved with beta-lactam-based siderophore conjugates targeting membrane associated penicillin binding proteins (PBPs) [7]. Cefiderocol (S-649266) is a beta-lactam–siderophore conjugate currently in phase III clinical trials which demonstrates enhanced potency against Gram-negative bacteria including

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• pathogen [10]. 3. Blocking adhesion and biofilm formation Bacterial adhesion to the host’s tissue is the initial step of every infection. In many cases, microbial adhesion is mediated by carbohydrate-binding proteins, so-called lectins, which recognize glycoconjugates on the surface of cells and tissue

• that, in addition to antimicrobial resistance, forms biofilms, a complex matrix of extracellular polysaccharides, polypeptides and DNA, which act as an additional protective barrier [30]. P. aeruginosa employs two lectins for biofilm formation and host–cell adhesion: proteins LecA and LecB [31][32

Impact of Pseudomonas aeruginosa quorum sensing signaling molecules on adhesion and inflammatory markers in endothelial cells

• Carmen Curutiu,
• Florin Iordache,
• Veronica Lazar,
• Aurelia Magdalena Pisoschi,
• Aneta Pop,
• Mariana Carmen Chifiriuc and
• Alina Maria Hoban

Beilstein J. Org. Chem. 2018, 14, 2580–2588, doi:10.3762/bjoc.14.235

• therapeutic strategies against P. aeruginosa infections, which are very difficult to treat. The vascular endothelium is crucial for cell and tissue homeostasis and regulation of inflammatory response. The loss of its integrity causes plasma, proteins and cells to build up in the interstitial space, resulting

• intercellular adherence junctions (AJ) and tight junctions (TJ), interconnected with cytoskeletal proteins. 3O-C12-HSL induces breaks in the epithelial barrier, disrupting cell junction and enhanced permeability by alterations in the phosphorylation status of TJ and AJ proteins [12]. The transmembrane protein

• cells [13]. ICAM-1 (intercellular adhesion molecule 1) and PECAM-1 (platelet endothelial cell adhesion molecule 1) are endothelial- and leukocyte-associated transmembrane proteins that permit transmigration of leukocytes into tissues and are induced by interleukins (IL-1, IL-8), tumor necrosis factor

Learning from B₁₂ enzymes: biomimetic and bioinspired catalysts for eco-friendly organic synthesis

• Keishiro Tahara,
• Ling Pan,
• Toshikazu Ono and
• Yoshio Hisaeda

Beilstein J. Org. Chem. 2018, 14, 2553–2567, doi:10.3762/bjoc.14.232

• ligand. B12 is reduced to Co(I) species in the active center by reductases in sustainable processes. The partially π-conjugated system of the corrin ring is less easy to be adducted by free radicals than those of porphyrins. B12 is bound to a number of proteins and acts as a module. Different chemical

Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids

• Eszter Lajkó,
• Sarah Spring,
• Rózsa Hegedüs,
• Beáta Biri-Kovács,
• Sven Ingebrandt,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226

• of phosphatidylinositol 3-kinase in the antitumor effects of conjugates Binding of GnRH or its conjugates to the GnRH-R receptor on tumor cells could stimulate different signaling elements (e.g., phosphatidylinositol 3-kinase – PI3K, mitogen-activated protein kinases) and effector proteins, which

Nucleoside macrocycles formed by intramolecular click reaction: efficient cyclization of pyrimidine nucleosides decorated with 5'-azido residues and 5-octadiynyl side chains

• Jiang Liu,
• Peter Leonard,
• Sebastian L. Müller,
• Constantin Daniliuc and
• Frank Seela

Beilstein J. Org. Chem. 2018, 14, 2404–2410, doi:10.3762/bjoc.14.217

• connectivity and gave an insight to the conformation. The sugar conformation (N vs S) in solution was different to that in the solid state. The macrocycles display free accessible Watson–Crick recognition sites valuable for base pairing with nucleic acids or proteins. Since the compact nucleoside macrocycles

The enzymes of microbial nicotine metabolism

• Paul F. Fitzpatrick

Beilstein J. Org. Chem. 2018, 14, 2295–2307, doi:10.3762/bjoc.14.204

• molybdopterin enzymes that also includes xanthine oxidoreductase and aldehyde oxidase [8]. Comparison of the pAO1 sequence with that of xanthine oxidoreductase identified ndhs, ndhm, and ndhl (initially designated ndhABC) as coding for three proteins: a 14.9 kDa subunit containing an iron–sulfur cluster, a 30

• kDa subunit with an FAD binding site, and an 87.7 kDa subunit containing the molybdopterin site, respectively [9][10]. Consistent with this identification, expression of the active enzyme required molybdopterin [9], and pAO1 contains a number of genes that have been identified as coding for proteins

• succinate semialdehyde and methylamine, mao. The expression of both proteins is regulated by nicotine [38][39], suggesting that both contribute in vivo. Mabo (γ-N-methylaminobutyrate demethylating oxidase) is similar in sequence to sarcosine dehydrogenase, and characterization of purified Mabo showed that

Dynamic light scattering studies of the effects of salts on the diffusivity of cationic and anionic cavitands

• Anthony Wishard and
• Bruce C. Gibb

Beilstein J. Org. Chem. 2018, 14, 2212–2219, doi:10.3762/bjoc.14.195

• account specific ion–ion interactions. To identify specific ion–ion interactions possibly contributing to the aggregation of proteins, we have used dynamic light scattering (DLS) to probe the aggregation of charged cavitands. DLS measurements of negatively charged 1 in the presence of a range of alkali

• akin to how these anions can partially unfold proteins. Alternatively, poorly solvated anions can also associate closely with cationic groups, induce charge neutralization, and engender aggregation and/or precipitation. In other words, they can also cause an apparent increase in the hydrophobic effect

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH

• Femke Beiroth,
• Tomas Koudelka,
• Thorsten Overath,
• Stefan D. Knight,
• Andreas Tholey and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163

• ; Introduction The investigation of the interactions between proteins and their ligands, such as lectins and carbohydrates, is of fundamental importance for the understanding of many biological processes. Several different methodologies are used for the elucidation of ligand–protein interactions. In addition to

• ]), we could not observe labeled products by fluorine NMR. This is presumably due to the low labeling efficiency as in the literature 19F NMR spectra were obtained with proteins having 19F-labeled amino acids incorporated [30]. Disappointingly, instead of crosslinking, we observed two different other

• standard method for FimH labeling. As we wish to eventually control bacterial adhesion by crosslinking of functional molecules to the adhesin (FimH), we will in the future utilize alternative labeling chemistry to efficiently target FimH. Experimental Peptides and proteins For photolabeling experiments

Synthesis and photophysical studies of a multivalent photoreactive Ru^II-calix[4]arene complex bearing RGD-containing cyclopentapeptides

• Sofia Kajouj,
• Lionel Marcelis,
• Alice Mattiuzzi,
• Adrien Grassin,
• Damien Dufour,
• Pierre Van Antwerpen,
• Didier Boturyn,
• Eric Defrancq,
• Mathieu Surin,
• Julien De Winter,
• Pascal Gerbaux,
• Ivan Jabin and
• Cécile Moucheron

Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150

• functionalized [54][55][56]. It is noteworthy that the calix[4]arene skeleton has been already exploited for the development of multivalent glyco- and peptidocalixarenes that can be recognized by cell-membrane receptors [57][58][59] and of calixarene derivatives able to specifically target membrane proteins

Design, synthesis and structure of novel G-2 melamine-based dendrimers incorporating 4-(n-octyloxy)aniline as a peripheral unit

• Cristina Morar,
• Pedro Lameiras,
• Attila Bende,
• Gabriel Katona,
• Emese Gál and
• Mircea Darabantu

Beilstein J. Org. Chem. 2018, 14, 1704–1722, doi:10.3762/bjoc.14.145

• s-triazine units (branch-cells, T-0 or cores T-2, Scheme 3 and Scheme 4). According to H. Kessler (in 1982, [62]), this parameter is appropriate for describing amide protons solvation in p→π conjugated systems, such as –N(H)–C(=O)– ↔ –N+(H)=C(–O−)– in peptides and proteins, in water. Later on (in

Natural and redesigned wasp venom peptides with selective antitumoral activity

• Marcelo D. T. Torres,
• Gislaine P. Andrade,
• Roseli H. Sato,
• Cibele N. Pedron,
• Tania M. Manieri,
• Giselle Cerchiaro,
• Anderson O. Ribeiro,
• Cesar de la Fuente-Nunez and
• Vani X. Oliveira Jr.

Beilstein J. Org. Chem. 2018, 14, 1693–1703, doi:10.3762/bjoc.14.144

• anticancer/antitumoral peptides according to the Database of Anticancer Peptides and Proteins (http://crdd.osdd.net/raghava/cancerppd/). Those AMPs with anticancer activity have been termed anticancer peptides (ACPs). Since their initial discovery, ACPs have constituted a promising alternative to

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• ; nucleoside; oligosaccharide; Introduction Nucleic acids and oligosaccharides are both mandatory polymers for the maintenance of life and cell growth. The former exists in nuclei and codes genetic information, which is transformed into proteins through a transcription process known as the “central dogma

• ” (i.e., DNA makes RNA makes proteins). The latter make up the cell walls of microorganisms and also play a role in transmitting information on the cell surface, whose interactions with proteins are a starting point for signal transduction into cells [1]. Since both types of polymers are essential for

Steric “attraction”: not by dispersion alone

• Ganna Gryn’ova and
• Clémence Corminboeuf

Beilstein J. Org. Chem. 2018, 14, 1482–1490, doi:10.3762/bjoc.14.125

• proteins [32], heteroaromatic cores that are the common building blocks for organic semiconductors [33], cyclophanes [34], Wilcox torsion balance systems [35], etc. The recognized importance of charge penetration in various chemical problems is paralleled by myriad developments aimed at accurately

Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions

• Anja Gronewold,
• Mareike Horn and
• Ines Neundorf

Beilstein J. Org. Chem. 2018, 14, 1378–1388, doi:10.3762/bjoc.14.116

• molecules is regulated, separates the nucleus from the cytosol. Macromolecules, like proteins, gain access to the nucleus by recognition of their nuclear localization sequences (NLS) by NLS-receptors, and following energy-dependent uptake processes. Several such natural occurring protein-derived NLS have

• or basic character. During the last 25–30 years, many different CPPs have been described and used for manifold applications like the delivery of nucleic acids, proteins, peptides, nanoparticles, small organic drugs, and others [10]. CPP conjugates can be generated by covalent conjugation between

Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

• Dan Liu,
• Ya-Li Guo,
• Jin Qu and
• Chi Zhang

Beilstein J. Org. Chem. 2018, 14, 1112–1119, doi:10.3762/bjoc.14.97

• , and it plays a crucial role in the elaboration and composition of biological systems. Amide bonds are widely present not only in peptides and proteins but also in pharmaceuticals and many natural products. Among the methods for amide bond formation, the direct condensation of carboxylic acids and

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• carrier of genetic information, the DNA double helix interacts with many natural ligands during the cell cycle, and is amenable to such intervention in diseases such as cancer biogenesis. Proteins bind DNA in a site-specific manner, not only distinguishing between the geometry of the major and minor

• interactions are also augmented by a series of electrostatic and van der Waals interactions including salt bridge formation with the phosphate backbone [1]. Although, the majority of proteins recognize DNA in the major groove due, in large part, to the potential and shape complementarity, several others also

• recognize the minor groove by sufficiently distorting the DNA structures leading to the opening of the minor groove [2]. In addition to the conventional direct and indirect readout mechanism, proteins have also been proposed to recognize the DNA minor groove by sensing variations in the shape and

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• exploited grinding to facilitate disaggregation of DNA from tightly bound proteins through selective denaturation of the latter. Despite the wide application of ball milling to amino acid chemistry, there have been limited reports of mechanochemical transformations involving nucleoside or nucleotide

• DNA and RNA isolation The lack of free-volume within double-stranded DNA at low hydration levels leads to limited ice formation even under cooling in liquid air [57]. In contrast, cold denaturation of globular proteins at such temperatures is almost ubiquitous [58]. Furthermore, large conformational

• ]. Dubinskaya reviewed early investigations into the grinding and stretching of polypeptides and proteins which showed rapid loss of enzyme activity at 80 K [101]. In contrast, more recent reports, in which both native and immobilised enzymes were ground at higher temperatures, demonstrated efficient

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• ]. The RGD motif is contained in various proteins like fibrinogen, fibronectin, prothrombin, tenascin and other glycoproteins [43] and is known to be recognized by over 10 integrins, among the over 24 known integrins [44][45], including all αv integrins, α5β1, α8β1 and αIIbβ3 [46]. The fact that

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• , peptidoglycans or lipopolysaccharides [1]. As part of glycoproteins they are involved in numerous biological processes. On the one hand, these macromolecules influence the proper folding of newly synthesized proteins in the intracellular compartment of the endoplasmic reticulum (ER). On the other hand