bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiangiogenic heparin-derived heparan sulfate mimics
Authors: Casu Benito , Naggi A. 
Published: October 2007

Abstract
Heparan sulfate (HS) is a glycosaminoglycan (GAG) widely distributed as a proteoglycan on the cell surface and in the extracellular matrix of animal tissues. Among other important physiological functions, its polysaccharide chains mediate cell proliferation by binding growth factors [fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF)], which are released in active form through the action of the enzyme heparanase overexpressed by tumor cells. HS is constituted of alternating disaccharide sequences of variously sulfated uronic acid (d-glucuronic, GlcA, or l-iduronic, IdoA) and glucosamine (N-acetylated, GlcNAc, or N-sulfated, GlcNSO3). HS mimics can be obtained by chemical modification of heparin, a more highly sulfated GAG clinically used as an anticoagulant and antithrombotic drug. With the aim of obtaining antagonists of FGFs as potential inhibitors of tumor neo-vascularization (angiogenesis), arrays of short FGF-binding sequences have been obtained by generating sulfation gaps within the prevalent (IdoA2SO3–GlcNSO36SO3)
n
sequences of heparin, by controlled base-catalyzed removal of 2-O-sulfate groups of IdoA2SO3 residues.The C(2)–C(3) bond of all nonsulfated uronic acid residues have then been split with periodate, to generate flexible joints along the polysaccharide chain. The novel heparin derivative (poly-PST.sU), chiefly made up of the repeating tetrasaccharide units –GlcNSO36SO3– IdoA2SO3– GlcNSO36SO3– sU– (where sU is a glycol-split and reduced uronic acid residue) binds FGF2 as strongly as heparin. However, it is a poor inducer of formation of FGF2 dimers and of complexes with FGF receptors, required for triggering mitogenic signals. NMR and molecular modeling studies indicate that formation of these higher-order complexes is prevented by the unfavorable conformation induced by glycol-split residues. In a parallel study, partially N-acetylated heparins have been obtained that efficiently inhibit heparanase upon glycol-splitting. It is noteworthy that glycol-splitting involves inactivation of the active site for antithrombin, with consequent loss of anticoagulant activity. In contrast, poly-PST.sU and some of its analogs show potent antiangiogenic activity in in vivo models in which heparin is either proangiogenic or inactive.
Semisynthesis and degradation of the tubulin inhibitors epothilone and tubulysin
Authors: Höfle G. , Glaser N. , Leibold T. , Karama U. , Sasse F. , Steinmetz H. 
Published: October 2007

Abstract
The structure-activity relationships of epothilones indicate that major modifications are only tolerated in the western ring segment. In particular, C2 methyl of the thiazole ring appears to be most flexible. Its broad modification started from epothilone F, which was obtained from natural epothilone B by hydroxylation via the N-oxide. Some of the prepared derivatives exhibit improved esterase stability in addition to high cytotoxic activity. For these and other favorable properties, amine (BMS-310705) was recently introduced in clinical trials. In an alternative approach, modified side chains were introduced by replacement of the C12,C15 ring segment via ring-opening olefin metathesis (ROM) of epothilone C in the presence of ethylene to 12,13-seco-epothilone C, introduction of a synthetic building block followed by ring-closing olefin metathesis (RCM), and epoxidation to the 16-alkyne analog of epothilone A.
The structure of the tetrapeptide tubulysin D was confirmed by total hydrolysis to N-methyl d-pipecolic acid, l-isoleucine, tubuvaline (Tuv), tubuphenylalanine (Tup), formaldehyde, and 3-methylbutyric acid. Mild acidic hydrolysis to cyclo-tubulysin andoxidative degradation to l-valine allowed the assignment of the stereocenters of Tuv, hydrazinolysis, and comparison with synthetic reference samples to that of Tup. The absolute configuration of tubulysin D is: (R)-Mep, (2,3S)-Ile, (1'R ,3'R)-Tuv, and (2S,4R)-Tup.
Synthesis of carbohydrate-based antibiotics
Authors: Wong C.-H. , Bryan M. C. , Nyffeler P. T. , Liu H. , Chapman Eli 
Published: October 2007

Abstract
Tackling the problem of carbohydrate recognition is a subject of current interest. Our strategies in this regard include development of new methods for the synthesis of saccharides and sugar arrays for screening, design of d-peptides to target bacterial cell-surface sugars, preparation of mechanism-based inhibitors of the enzymes involved in the biosynthesis of saccharides and the synthesis of aminoglycoside mimetics to target RNA.
DNA minor-groove binders. Design, synthesis and biological evaluation of ligands structurally related to CC-1065, distamycin, and anthramycin
Authors: Baraldi P. G. , Tabrizi M. A. , Preti D. , Fruttarolo Francesca , Avitabile Barbara , Bovero Andrea , Pavani G. , del Carretero M. Carmen Nunez , Romagnoli R. 
Published: October 2007

Abstract
Many natural and synthetic anticancer agents with the ability to interact with DNA have been discovered, but most have little sequence-specificity and often exhibit severe toxicity to normal tissues. Thus, there has been considerable interest in molecular biology and human medicine to find small molecules that can alkylate the DNA in a sequence-specific manner and modify the function of nucleic acids irreversibly. Analogs of naturally occurring antitumor agents, such as distamycin A, which bind in the minor groove of DNA, represent a new class of anticancer compounds currently under investigation. Distamycin A has driven researchers' attention not only for its biological activity, but also for its nonintercalative binding to the minor groove of double-stranded B-DNA, where it forms a strong reversible complex preferentially at the nucleotide sequences consisting of 4-5 adjacent adenine-thymine (AT) base pairs. The pyrrole-amide skeleton of distamycin A has been also used as DNA sequence-selective vehicles for the delivery of alkylating functions to DNA targets, leading to a sharp increase of its cytotoxicity, in comparison to that, very weak, of distamycin itself.
In the last few years, several hybrid compounds, in which derivatives of naturally occurring antitumor agents, such as anthramycin or the alkylating unit of the antibiotic CC-1065, have been tethered to distamycin frames. The DNA alkylating and cytotoxic activities against several tumor cell lines are reported and discussed in terms of their structural differences in relation to both the number of N-methyl pyrrole rings and the type of alkylating unit tethered to the oligopeptidic frame.
HIV-1 integrase inhibitors that block HIV-1 replication in infected cells. Planning synthetic derivatives from natural products
Authors: Di Santo Roberto , Costi Roberta , Artico Marino , Tramontano E. , Colla P. La , Pani A. 
Published: October 2007

Abstract
Combination therapy using reverse transcriptase (RT) and protease (PR) inhibitors is currently the best clinical approach in combatting acquired immunodeficiency syndrome (AIDS), caused by infection from the human immunodeficiency virus type 1 (HIV-1). However, the emergence of resistant strains calls urgently for research on inhibitors of further viral targets such as integrase (IN), the enzyme that catalyzes the integration of the proviral DNA into the host chromosomes. Recently, we started studies on new IN inhibitors as analogs of natural products, characterized by one or two 3,4-dihydroxycinnamoyl moieties, which were proven to be IN inhibitors in vitro. Then, we designed and synthesized a number of derivatives sharing 3,4 dihydroxycinnamoyl groups, obtaining potent IN inhibitors active at submicromolar concentrations. Unfortunately, these derivatives lacked antiretroviral activity, probably owing to their high cytotoxicity. So we designed a number of 3,4,5-trihydroxycinnamoyl derivatives as less-cytotoxic IN inhibitors, which were proven to be antiretrovirals in cell-based assays. Finally, we designed and synthesized a number of aryldiketohexenoic acids, strictly related to the aryldiketo acid series recently reported by Merck Company, which were shown to be potent antiretroviral agents endowed with anti-IN activities either in 3' processing or in strand transfer steps.
New and old challenges in total synthesis. From concept to practice
Authors: Hanessian S. , Margarita Roberto , Hall Adrian , Johnstone Shawn , Tremblay M. , Parlanti L. 
Published: October 2007

Abstract
The total synthesis of dysinosin A, a novel member of the aeruginosin group of marine natural products is discussed. The stereocontrolled synthesis also confirms the proposed structure and absolute stereochemistry of the natural product.
Chemoenzymatic methods for the enantioselective preparation of sesquiterpenoid natural products from aromatic precursors
Authors: Banwell M. G. , Edwards A. J. , Harfoot G. J. , Jolliffe K. A. , McLeod M. D. , McRae K. J. , Stewart S. G. , Vögtle M. 
Published: October 2007

Abstract
The enantiomerically pure cis-1,2-dihydrocatechols 2, which are generated by enzymatic dihydroxylation of the corresponding aromatic, engage in regio- and stereo-controlled Diels-Alder cycloaddition reactions to give a range of synthetically useful bicyclo[2.2.2]octenes. Certain examples of the latter type of compound have been used as starting materials in the synthesis of the sesquiterpenoids (−)-patchoulenone and (−)-hirsutene.
Progress in fumagillin synthesis
Authors: Picoul W. , Bedel O. , Haudrechy A. , Langlois Y. 
Published: October 2007

Abstract
After a brief account of the syntheses previously described in literature, several approaches of the antiangiogenic sesquiterpene fumagillin are described. Particularly, a Claisen–Ireland ring-closing metathesis strategy allowed the stereoselective preparation of several advanced intermediates in the fumagillin synthesis.
Total syntheses of 11-deoxytetrodotoxin and 8,11-dideoxytetrodotoxin
Authors: Nishikawa T. , Urabe D. , Yoshida K. , Iwabuchi Tomoko , Asai Masanori , Isobe M. 
Published: October 2007

Abstract
11-Deoxytetrodotoxin and 8,11-dideoxytetrodotoxin were synthesized from the same intermediate in the enantiomerically pure form.
Biomimetic approach toward the stereoselective synthesis of acetogenins
Authors: Orru R. V. A. , Groenendaal Bas , van Heyst J. , Hunting Mark , Wesseling C. , Schmitz R. F. , Mayer S. F. , Faber K. 
Published: October 2007

Abstract
Acetogenins isolated from the Annonaceae family of tropical trees have drawn considerable attention owing to their broad spectrum of biological activities. They are structurally characterized by the presence of one to three tetrahydrofuran rings in the center of a long (partly hydroxylated) hydrocarbon chain that ends in a (functionalized) butenolide moiety. Here we describe some of our results toward the first asymmetric total synthesis of cis-gigantrionenin, a principal acetogenin. In this approach, an enzyme-catalyzed epoxide hydrolysis and an enzyme-triggered double cyclization are crucial and give stereoselective access to essential chiral building blocks.
Microencapsulated methylrhenium trioxide (MTO)/H2O2 systems for the oxidation of cardanol derivatives
Authors: Saladino R. , Mincione E. , Attanasi O. A. , Filippone Paolino 
Published: October 2007

Abstract
A convenient and efficient application of microencapsulated/methylrhenium trioxide (MTO) and MTO/pyridine systems for the selective oxidation of cardanol derivatives is reported. Environmentally friendly and low-cost H2O2 was used as the oxygen atom donor. The catalysts were stable systems for at least five recycling experiments. In the oxidation of C2 alkyl-substituted cardanol derivatives, high conversion and yields of the corresponding para-benzoquinones were obtained. By contrast, in the absence of the C2 substituent, an unprecedented oxidative degradation to di-γ-lactone derivative was observed.
Enantioselective synthesis and biological evaluation of a-hydroxylated lactone lignans
Authors: Sefkow M. , Raschke M. , Steiner C. 
Published: October 2007

Abstract
A short and efficient synthesis of enantiomerically pure α-hydroxylated lactone lignans starting from commercially available diisopropyl malate is presented. Stereoselective alkylation with various benzyl bromides and saponification yielded the corresponding succinic acids. Acetalization afforded the dioxolanones, which were stereoselectively alkylated. Reduction (and deprotection, where required) yielded the lactone lignans in up to 30 % overall yield. The inhibition of the proliferation of HT29 colon cancer cells was investigated. One lignane, bis-2,4,6 trimethylbenzyllactone lignan, was active (IC50 = 35 μM), whereas all other tested lignans were inactive within the investigated concentration range.
Stereocontrolled construction of conformationally constrained and rigid bis(a-amino acid) derivatives
Authors: Undheim K. , Efskind Jon , Hoven G. B. 
Published: October 2007

Abstract
Cystine is regarded as a four-atom bridged bis(α-amino acid). The bridge between the two glycine moieties in cystine has been replaced with all-carbon C4-bridges between the α-carbon of the glycines. The products are dicarba analogs of cystine. Conformational constraints have been conferred on these molecules by insertion of cis- and trans- double bonds in the bridge, by alkylidene substituents, by insertion of a triple bond, by insertion of aromatic or heteroaromatic rings, or otherwise by ring formation. Particularly rigidified dicarba analogs of cystine have been prepared where the α-amino acid carbon is quaternary and part of tricyclic ring structures. Ru(II)-catalyzed ring-closing metathesis (RCM) reactions have been widely used in the preparation of cyclic amino acids. Conformational constraints in acyclic structures result from substitution by simple alkyl, alkenyl, or alkynyl groups at the α-amino acid carbon in the formation of α-quaternary amino acid derivatives.
Stereochemical analysis of natural products. Approaches relying on the combination of NMR spectroscopy and computational methods
Authors: Riccio R. , Bifulco Giuseppe , Cimino Paola , Bassarello Carla , Gomez-Paloma Luigi 
Published: October 2007

Abstract
The stereochemical study of flexible stereogenic carbon chains, such as those of many novel natural products, is a particularly challenging task. Recent applications of our group on the so-called "J-based approach", a methodology relying on a detailed analysis of homonuclear (H-H) and heteronuclear (C-H) 2,3
J couplings, include the study of the sphinxolide family of antitumor macrolides, a group of molecules characterized by a flexible macrocyclic framework bearing a number of oxygenated and methylated undetermined stereocenters, and of ascaulitoxin, a nitrogen-containing phytotoxin with herbicidal activity produced by a phytopathogenic fungus. An extension of the original procedure, relying on a Hartree-Fock (HF) ab initio calculation of conformational equilibrium and an estimate of the Boltzmann averaged 2,3
JHH and 2,3
JCH couplings, has been applied to the stereochemical study of sapinofuranone A, where the conformational equilibrium among existing rotamers had initially led to controversial results. 13C NMR chemical shifts are additional useful parameters in the study of complex organic molecules. Along these lines, we have lately proposed the use of Hartree–Fock gauge including atomic orbitals (GIAO) calculated 13C NMR chemical shift values as a supporting tool for the validation of the structure of new natural products and the determination of the relative stereochemistry of diastereomeric flexible compounds that are characterized by multiple conformer equilibria.
Exploitation of proteomics strategies in protein structure-function studies
Authors: Marino Gennaro , Pucci P. , Birolo Leila , Ruoppolo M. 
Published: October 2007

Abstract
Mass spectrometry plays a central role in structural proteomics, particularly in highly intensive structural genomics projects. This review paper reports some examples taken from recent work from the authors' laboratory and is aimed at showing that modern proteomics strategies are instrumental in the integration of structural genomic projects in fields such as: (i) protein–protein interactions, (ii) protein-DNA interactions, (iii) protein–ligand interactions, and (iv) protein-folding intermediates.
Prion protein allotype profiling by mass spectrometry
Authors: Schininà M. E. , Maras Bruno , Cardone Franco , Mancone Carmine , Principe S. , Di Bari M. A. , Parchi P. , Pocchiari M. 
Published: October 2007

Abstract
Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative pathologies characterized by the formation in the central nervous system of the amyloid protein PrPSc, which derives from a cellular precursor called PrPc. Epidemiological and laboratory studies have shown that in species where the PrPc gene is polymorphic, the genotype composition is an important factor for the development of the disease. Identification of PrPSc allotypes accumulated in the brain during the disease proved valuable to investigate whether these polymorphisms are critical for the pathological conversion. These analyses are complicated by the heterogeneity and the insolubility of the prion amyloid extracted from affected brains, which have been obviated by extensive digestion of extracted fractions and analysis of peptide fragment composition. We have developed an optimized protocol of liquid chromatography/mass spectrometry (LC/MS) that can reliably map PrP peptides in digested fractions with a low PrPSc/contaminants ratio. This approach has been successfully applied to the analysis of amyloidogenesis in experimentally infected PrP-heterozygous laboratory animals.
Toxins from Adriatic blue mussels. A decade of studies
Authors: Ciminiello Patrizia , Dell'Aversano Carmela , Fattorusso Ernesto , Forino Martino , Magno Silvana 
Published: October 2007

Abstract
A research program was initiated in 1990 to carefully examine the toxin profiles in mussels from the northern Adriatic Sea. Since then, a number of polyether toxins have been isolated and characterized, some of which represent new additions to the diarrhetic shellfish poisoning (DSP) class of biotoxins and seem to be peculiar to the Adriatic Sea. During our investigation of toxic Adriatic mussels, we also isolated a new type of toxin, whose structure was elucidated by extensive use of 1D and 2D NMR techniques. Some of them could represent a further alarm for public health owing to their cytotoxic activity. The recent application of liquid chromatography/mass spectrometry (LC/MS) methods for detection of Adriatic marine biotoxins allowed us to hasten the analysis of toxic samples and to advance effective structural hypothesis even when full structure elucidation of new toxins by NMR spectroscopy is hampered by the limited amount of available material.
Bioactive macrolides and polyketides from marine dinoflagellates
Authors: Kobayashi J. , Shimbo K. , Kubota Takaaki , Tsuda M. 
Published: October 2007

Abstract
Absolute stereochemistry of amphidinolides G and H, potent cytotoxic 27- and 26-membered macrolides, respectively, isolated from a marine dinoflagellate Amphidinium sp., was determined by X-ray diffraction analysis, synthesis of a degradation product, and chemical interconversion. Six new macrolides, amphidinolides H2~H5, G2, G3, and W, have been isolated from a marine dinoflagellate Amphidinium sp. (strain Y-42), and the structures were elucidated by 2D NMR data and chemical means. The structure-activity relationship of amphidinolide H-type macrolides for cytotoxicity was examined. The biosynthetic origins of amphidinolides B, C, H, J, T1, and W were investigated on the basis of 13C NMR data of 13C-enriched samples obtained by feeding experiments with [1-13C], [2-13C], and [1,2-13C2] sodium acetates in cultures of the dinoflagellates. Five novel long-chain polyhydroxyl compounds, colopsinols A~E, were obtained from the Amphidinium sp. (strain Y-5).
Detection of pharmacologically active natural products using ecology. Selected examples from Indopacific marine invertebrates and sponge-derived fungi
Authors: Proksch P. , Ebel R. , Edrada R. A. , Schupp P. , Lin W. H. , Sudarsono  , Wray V. , Steube K. 
Published: October 2007

Abstract
This review article presents our group's recent research findings with regard to bioactive natural products from marine sponges and tunicates, as well as from sponge derived fungi. The organisms discussed originate in the Indopacific region, which has an exceptionally rich marine biodiversity. Major topics that are covered in our review include the chemical ecology of sponges, focusing on defense against fishes, as well as the isolation and identification of new bioactive constituents from sponges and tunicates. Sponge derived fungi are introduced as an emerging source for new bioactive metabolites, reflecting the currently growing interest in natural products from marine microorganisms.
Chemical studies on plant leaf movement controlled by a biological clock
Authors: Ueda M. , Sugimoto T. , Sawai Y. , Ohnuki T. , Yamamura Shosuke 
Published: October 2007

Abstract
Most leguminous plants close their leaves in the evening, as if to sleep, and open them early in the morning according to the circadian rhythm controlled by a biological clock. Extensive studies on nyctinastic plants led to the isolation of a variety of leaf-closing and -opening substances. And we found that the biological clock regulates the balance of concentration between leaf-opening and -closing substances in the plant body during the day.
Structural flexibility of hyaluronan oligomers as probed by molecular modelling
Authors: Tafi A. , Manetti Fabrizio , Corelli Federico , Alcaro Stefano , Botta Maurizio 
Published: October 2007

Abstract
In the last few years, molecular modeling studies have been published that are devoted to a better understanding of the structural flexibility of hyaluronan (HA). Further conformational investigations, however, are needed on this polysaccharide, such as the application of statistical methods to perform enhanced one-step conformational analyses of its subunits. Moreover, the adjustment of assisted model building and energy refinement (AMBER) force field could provide the appropriate computational tool to study the interactions of HA and its derivatives with proteins. The present paper reports a combined Monte Carlo (MC) and molecular dynamics (MD) approach applied to the conformational study of HA, using an adjusted version of AMBER force field and the generalized Born solvent-accessible surface area (GB/SA) continuum solvation model. The MC approach turned out to be extremely effective to outline a conformational survey of the disaccharides constituting HA. Complete sets of conformations of the monomers were provided for the first time, some of which had never been predicted. MD technique, integrating the MC results, correctly reproduced the unusual stiffness of HA and predicted the existence of a minor skew-boat conformation of the β-d-glucuronic moiety. The computational approach, as a whole, improved the comprehension of the dynamic behavior of HA and offered a clear causal explanation of the relative dynamics of the glycosidic linkages.