Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• -based approach, which aim to trigger the production of specific and functional antibodies that prevent initial infection limiting pathogen/viral dissemination. Recent publications suggest that many different aspects are becoming clear and have to be underlined. The design of anti HIV-1 vaccines depends

• on the identification of sugar epitopes of the surface envelope glycoprotein of HIV-1, capable of eliciting a protective response. GAuNPs coated with high-mannose type oligosaccharide of HIV-1 gp120, were prepared as glycoconjugate systems able to mimic the natural presentation of gp-120 high-mannose

• glycans. It was demonstrated that they were able to inhibit DC-SIGN-mediated HIV-1 infections and to interfere with the antibody/gp120 binding process. Most of these systems proved able to elicit the production of carbohydrate-specific antibodies in animals, though the generated IgGs turned out to be

Revaluation of biomass-derived furfuryl alcohol derivatives for the synthesis of carbocyclic nucleoside phosphonate analogues

• Bemba Sidi Mohamed,
• Christian Périgaud and
• Christophe Mathé

Beilstein J. Org. Chem. 2017, 13, 251–256, doi:10.3762/bjoc.13.28

• transposition giving rise to carbocyclic nucleoside phosphonates having structural similarity with carbonucleosides belonging to the neplanocin family. All the newly synthesized compounds were evaluated for their antiviral properties against HIV-1, Zika virus, Dengue-2 virus, HSV-1, HSV-2 and Chikungunya virus

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

• membrane proteins where membrane permeability is considered to be important for drugs to be useful [10][11]. Successes have been reported for SBDD and it has contributed to many compounds reaching clinical trials and get FDA approvals to go into the market [12]. HIV-1 (Human Immunodeficiency Virus I

• longer than they could have without the treatment [13][14]. Saquinavir is one of the first HIV-1 protease targeted drugs to reach the market (Figure 2a and 2c) [15]. Amprenavir is another drug that was developed to target HIV-1 protease that was also developed influenced by SBDD (Figure 2b and 2d) [16

• phosphate probe which are used to identify the binding sites for drug-like molecules and phosphorylated ligands (such as ATP) respectively [92]. The best ligand binding site identified in HIV-1 protease by SiteHound is shown in Figure 4. This ligand binding site is the known inhibitor binding site in HIV-1

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

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• atom in the chain, and 10 possessing several ethylene glycol moieties were used to increase the solubility of modified polyamides in water. Selection of the target DNA and design of TFOs and MGBs The polypurine tract of the HIV-1 provirus is a valuable target for MGB-TFO conjugates [35]. It has a 16-bp

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• formed by the head-to-tail cyclisation of two nonapeptides that are themselves derived from the C-terminal region of precursor peptides, and both heterodimers or homodimers can be formed in this process [84][144]. Along with their antimicrobial activity, these peptides can inhibit fusion of HIV-1 to host

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• applied to the synthesis of a drug candidate, which had been proved to possess better inhibitory activity than efavirenz against HIV-1 reverse transcriptase [19]. Besides, the reactions may provide an efficient route to the optically pure propargylic alcohols. Ir-catalyzed synthesis of 3-hydroxyoxindoles

A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• ligand, bound in the groove of the HIV-1 frameshift site (FS), and (3) the (CUG)6 X-ray and HIV-1 FS NMR structures were both A-form and similar suggesting replacement of the ammonium ions in DB213 with triaminotriazine units. Ligand 30 was studied in collaboration with both Anne Baranger and Paul

Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A

• Ana Čikoš,
• Irena Ćaleta,
• Dinko Žiher,
• Mark B. Vine,
• Ivaylo J. Elenkov,
• Marko Dukši,
• Dubravka Gembarovski,
• Marina Ilijaš,
• Snježana Dragojević,
• Ivica Malnar and
• Sulejman Alihodžić

Beilstein J. Org. Chem. 2015, 11, 1447–1457, doi:10.3762/bjoc.11.157

• sponges, which display extraordinary antitumor activity [29]. At the same time, the spiroketal-containing integramycin acts as an HIV-1 protease inhibitor [27]. The studies of Hayashi et al. have shown that the integrity of the spiroketal subunit is essential for the inhibition of telomerase by

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• various DNA and RNA. The ability of ethidium bromide analogues to inhibit the HIV-1 Rev–Rev Response Element (RRE) interaction, as well as their affinity to calf thymus (ct)DNA was analysed. One derivative (Figure 2, 1) displayed an enhanced affinity for HIV-1 RRE and a lower DNA affinity (i.e., lower

• respect to other nucleotides. In addition, the observed selectivity towards poly(G) and poly(A) can be beneficial in biological applications for instance to influence the mRNA-function via binding to the poly(A) tail [62][63][64] and inhibition of the HIV-1 replication by targeting recognition of the

Encapsulation of biocides by cyclodextrins: toward synergistic effects against pathogens

• Véronique Nardello-Rataj and
• Loïc Leclercq

Beilstein J. Org. Chem. 2014, 10, 2603–2622, doi:10.3762/bjoc.10.273

Glycosystems in nanotechnology: Gold glyconanoparticles as carrier for anti-HIV prodrugs

• Fabrizio Chiodo,
• Marco Marradi,
• Javier Calvo,
• Eloisa Yuste and
• Soledad Penadés

Beilstein J. Org. Chem. 2014, 10, 1339–1346, doi:10.3762/bjoc.10.136

• virus type-1 (HIV-1) [1] continues to be a major leading pandemic disease worldwide with approximately 34 million people living with HIV [2]. Due to its incredible genetic variance and the specificity for CD4+ T cells, this virus is responsible for 800.000 deaths per year. In addition to sexual

• related to HIV envelope [18]. GNPs coated with oligomannosides of the gp120 (manno-GNPs) were able to inhibit the DC-SIGN-mediated HIV-1 trans-infection of human T-cells [19] and gold glyconanoparticles coated with sulfated ligands showed to interfere with the adhesion/fusion of HIV during its entry [20

• nucleoside substrates acting as chain terminators in the DNA polymerisation reaction catalyzed by HIV-1 RT [3]. Both drugs were transformed in ester derivatives to prepare the GNPs. The pH-mediated release of the drugs from the GNPs surface was evaluated and cellular experiments demonstrated that abacavir

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• - [31], elastase- [32][33][34][35], and HIV-1 protease [36] and papain [37]. For the design of β-lactams, the Staudinger reaction involving a [2 + 2] cycloaddition of ketenes and imines is the most common method used [38]. However, Ugi reactions starting form β-amino acids are also described. In 2002

• of amide bonds by 1,2,3-triazoles, especially the 1,4-disubstituted isomer, provided a wide variety of biological active peptidomimetics. Peptidomimetics containing these triazole cores can serve as blood components [77], anticancer medications [78], inhibitors of cysteine [79] and HIV-1 proteases

• ]. Several studies have revealed the bio-similarity of triazoles with amide bonds. For example, X-ray studies towards triazole based-mimics of the HIV-1 protease inhibitor amprenavir showed an equivalent binding mode with the protease active site as compared to the amide-bond inhibitor [81][83][84

Investigating the continuous synthesis of a nicotinonitrile precursor to nevirapine

• Ashley R. Longstreet,
• Suzanne M. Opalka,
• Brian S. Campbell,
• B. Frank Gupton and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2013, 9, 2570–2578, doi:10.3762/bjoc.9.292

• ; nicotinonitriles; Introduction Nevirapine (3) was the first commercially available non-nucleoside reverse transcriptase inhibitor (NNRTI), and has remained an important medicine in the management of human immunodeficiency virus (HIV) [1][2]. Nevirapine combined with lamivudine (3TC) and azidothymidine (AZT) or

Synthesis of the spiroketal core of integramycin

• Evgeny. V. Prusov

Beilstein J. Org. Chem. 2013, 9, 2446–2450, doi:10.3762/bjoc.9.282

• ; hydrozirconation; natural products; spiroketals; total synthesis; Findings Integramycin is a polyketide natural product isolated from Actinoplanes sp. by the Singh group at Merck [1] (Figure 1). The compound was found to inhibit HIV-1 integrase coupled strand transfer reactions with IC50 values of 3 and 4 μM

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• , Vedejs), the convergent approach reported by Myers allows a modular entry to diverse members of the cytochalasin alkaloid family [68]. As proof of concept, the macrolactone cytochalasin B (52) and the carbocyclic cytochalasin L-696,474 (78), a potent HIV-1 protease inhibitor [69][70][71][72], were

• interesting biological properties, such as high antiviral activity (156) [141], inhibition of the HIV-1 protease (157) [132], antibacterial and antifungal activities (159–160) [133] or neuritogenic properties (161) [134]. So far, only a few total syntheses were accomplished and the exact biosynthetic pathways

Facile synthesis of benzothiadiazine 1,1-dioxides, a precursor of RSV inhibitors, by tandem amidation/intramolecular aza-Wittig reaction

• Krishna C. Majumdar and
• Sintu Ganai

Beilstein J. Org. Chem. 2013, 9, 503–509, doi:10.3762/bjoc.9.54

• activity [16][17][18][19][20][21][22], including hypoglycemic (1), anti-HIV (2), HIV-1 specific non-nucleoside reverse transcriptase inhibitor (3), sedative (4), and respiratory syncytial virus (RSV) inhibitory activity (5; Figure 1). A literature search revealed that the 1,2,4-benzothiadiazine 1,1

Tricyclic flavonoids with 1,3-dithiolium substructure

• Lucian G. Bahrin,
• Peter G. Jones and
• Henning Hopf

Beilstein J. Org. Chem. 2012, 8, 1999–2003, doi:10.3762/bjoc.8.226

• unit. In addition to this, they are known to possess anti-inflammatory activity, inhibit the lens-aldose reductase, and decrease the blood glucose level [11][12]. Moreover, compound 3 was shown to inhibit HIV-1 integrase [13][14]. Several molybdenum and tungsten oxobisdithiolene complexes have been

Peptides presenting the binding site of human CD4 for the HIV-1 envelope glycoprotein gp120

• Julia Meier,
• Kristin Kassler,
• Heinrich Sticht and
• Jutta Eichler

Beilstein J. Org. Chem. 2012, 8, 1858–1866, doi:10.3762/bjoc.8.214

• Based on the structure of the HIV-1 glycoprotein gp120 in complex with its cellular receptor CD4, we have designed and synthesized peptides that mimic the binding site of CD4 for gp120. The ability of these peptides to bind to gp120 can be strongly enhanced by increasing their conformational stability

• protein binding site mimics. We have previously developed strategies for the design and generation of scaffolded and assembled peptides to generate protein binding site mimics [1]. The interaction of the HIV-1 envelope glycoprotein gp120 with its cellular receptor CD4 is the first step in the process of

• entry of the virus HIV-1 into its host cell. A range of crystal structures of the gp120–CD4 complex [2][3][4][5][6] have provided information on the structural details of the gp120–CD4 interaction and, thus, the basis for a rational design of inhibitors. Later on, it was found that the epitopes of a

Molecular solubilization of fullerene C₆₀ in water by γ-cyclodextrin thioethers

• Hai Ming Wang and
• Gerhard Wenz

Beilstein J. Org. Chem. 2012, 8, 1644–1651, doi:10.3762/bjoc.8.188

• synthesized and utilized for the inhibition of therapeutically important enzymes, such as HIV-1 protease [12], for the prevention of bacterial growth [13][14], or for photodynamic therapy of cancer by scission of DNA [3]. Despite these successes, there are still several issues relating to the chemical

Design of a novel tryptophan-rich membrane-active antimicrobial peptide from the membrane-proximal region of the HIV glycoprotein, gp41

• Evan F. Haney,
• Leonard T. Nguyen,
• David J. Schibli and
• Hans J. Vogel

Beilstein J. Org. Chem. 2012, 8, 1172–1184, doi:10.3762/bjoc.8.130

• that does not possess intrinsic antimicrobial activity. Peptides derived from the envelope HIV-1 glycoproteins, gp120 and gp41, have previously been examined for their antimicrobial activity [10] and we chose to use the membrane-proximal region of gp41 as our starting peptide scaffold. This region of

• has four additional positive charges and is also antimicrobially inactive. The lack of antimicrobial activity may be related to the fact that the gp41w peptide appears to oligomerize in solution. When found in the HIV-1 Env glycoprotein complex, gp41 is known to exist as a trimer [26], and previous

Marilones A–C, phthalides from the sponge-derived fungus Stachylidium sp.

• Celso Almeida,
• Stefan Kehraus,
• Miguel Prudêncio and
• Gabriele M. König

Beilstein J. Org. Chem. 2011, 7, 1636–1642, doi:10.3762/bjoc.7.192

• liver stages as described by Ploemen et al. [24]. Inhibition of the viral HIV-1- and HIV-2-induced cytopathogenic effect in MT-4 cells assays was performed according to Pannecouque et al. [25] and Zhan et al. [26]. Severe Acute Respiratory Syndrome coronavirus (SARS) assays were performed according to

• Phosphorylation & Disease, CNRS, Roscoff, France) for performing the protein kinases assays and Dr. C. Pannecouque (Rega Institute for Medical Research, Leuven, Belgium) for performing the HIV-1 and HIV-2 antiviral assays; we also kindly thank Indra Bergval (KIT Biomedical Research, Royal Tropical Institute

Multicomponent synthesis of artificial nucleases and their RNase and DNase activity

• Anton V. Gulevich,
• Lyudmila S. Koroleva,
• Olga V. Morozova,
• Valentina N. Bakhvalova,
• Vladimir N. Silnikov and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2011, 7, 1135–1140, doi:10.3762/bjoc.7.131

• oligoribonucleotides and an HIV-1 recombinant RNA fragment 96 nucleotides long [17]. Previously, compounds 1 and 2 have been synthesized from the corresponding diamines by condensation with protected natural amino acids and subsequent deprotection [18]. This approach is significantly limited by using available natural

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

Approaches towards the synthesis of 5-aminopyrazoles

• Ranjana Aggarwal,
• Vinod Kumar,
• Rajiv Kumar and
• Shiv P. Singh

Beilstein J. Org. Chem. 2011, 7, 179–197, doi:10.3762/bjoc.7.25

• = SCH3), respectively. These compounds were further treated with nitrous acid and coupled with different secondary amines to yield the triazenopyrazoles 78. Compounds 78 were tested for biological activity against HIV-1 and herpes simplex viruses, and showed moderate activity against HIV-1 virus (Scheme