Lysyl oxidase dependent synthesis of a collagen cross-link containing histidine

To date, collagen appears unique among proteins in that it contains histidine in certain of its cross-links. Synthesis of histidine containing collagen cross-links was studied in vitro with lathyritic L-¹⁴C histidine or L-¹⁴C lysine labelled bone collagen fibrils and purified lysyl oxidase. Synthesis of the tetrafunctional cross-link, dehydrohistidinohydroxymerodesmosine occurred with lysyl oxidase and was inhibited by β-aminopropionitrile. Synthesis began after a lag period of sixteen hours and then proceeded linearly for four days. These data indicate that enzyme dependent synthesis of dehydrohistidinohydroxymerodesmosine occurs in vitro in a biochemically defined system. Biosynthesis in vivo might occur under similar conditions.     

Synthesis of a Nucleoside Bioconjugate System as a Potential Anti-HIV Agent

Abstract

Synthesis and anti-HIV data for a bioconjugate molecule incorporating a HIV protease inhibitor (A74704) and a HIV RT inhibitor (d4T) are presented.     

Polymers of 3-hydroxyacids in plants

Polyhydroxyalkanoates (PHA) are polyesters of bacterial origin that have properties of biodegradable plastics and elastomers. Synthesis of PHA in crop plants would allow the large-scale production and use of these biodegradable and renewable polymers as substitutes for petroleum-derived plastics. Synthesis of a diversity of PHAs in plants, such as Arabidopsis thaliana, rapeseed, corn and cotton, has been demonstrated through the genetic engineering of metabolic pathways in the cytoplasm, plastid and peroxisome. PHA can also be used as a novel tool to study various aspects of plant metabolism, such as the regulation of carbon flux to the fatty acid biosynthetic and degradation pathways.     

Production of a novel bioflocculant by fed-batch culture of Citrobacter sp.

Production of a novel bioflocculant by a fed-batch culture of Citrobacter sp. TKF04 was investigated using acetic acid as a sole carbon source. Synthesis of the bioflocculant was favored by dissolved O₂ tension at 20% of air saturation and C/N ratio (mol acetic acid/mol ammonium) of 10:1 in the feed solution. Under optimal conditions, 4.6 g crude bioflocculant per liter broth was produced, whose flocculating activity was 22 300 units. This activity was 9 times higher than that of the control (only acetic acid was supplied).     

Preparation and anticoagulant activity of a low-molecular-weight sulfated chitosan

Synthesis of chitosan sulfates with low molecular weight (M_v 9000–35,000 Da) was carried out by sulfation of low molecular weight chitosan (M_v 10,000–50,000 Da). The oleum was used as sulfating agent and dimethylfornamide as medium. The chitosans were prepared by enzymatic and acidic hydrolysis of initial high molecular weight chitosan as well as by extrusion solid-state deacetylation of chitin. As was shown by FT-IR and NMR-methods and elemental analysis, the sulfation occurred at C-6 and C-3 positions and substitution degree is 1.10–1.63. The molecular weight sulfated chitosan was determined by viscometric method and the Mark–Houwink equation [η]=10⁻⁵ 4.97 M^0.77. Study of anticoagulant activity showed that chitosan sulfates with lowered molecular weight demonstrated a regular increase of anti-Xa activity like heparins.     

Synthesis of a tetrasaccharide fragment of cobra venom factor oligosaccharide.

Synthesis of a tetrasaccharide fragment, alpha-L-Fuc-(1-->3)-beta-D-GlcNAc-(1-->2)-alpha-D-Man-(1-->6)-alpha-D-Man- OMe of the cobra venom factor (CVF) oligosaccharide is described.     

Structure-activity relationship studies on a series of cyclohexylpiperazines bearing a phanylacetamide as ligands of the human melanocortin-4 receptor

Synthesis and structure-activity relationship studies of a series of cyclohexylpiperazines bearing an amide side chain as ligands of the MC4 receptor are discussed. Compounds such as 11i from this series are potent agonists (EC(50)=33nM, IA=96%).     

Induction of protein synthesis in response to ultraviolet light,nalidixic acid and heat shock in the cyanobacterium Phormidium laminosum

Synthesis of three polypeptides (43, 34 and 26 kDa) was enhanced or induced in the thermophilic cyanobacterium Phormidium laminosum following irradiation with UV light. Synthesis of several polypeptides was also enhanced/induced following treatment with nalidixic acid. Three had similar molecular masses to those induced by UV. One of these (43 kDa) was also apparently enhanced following prolonged heat shock, as were a number of other polypeptides with a wide range of molecular masses. The specific induction of the 34 and 26 kDa polypeptides following DNA damage and inhibition of replication suggests that they may be involved in DNA repair and, possibly, also in recombination.     

Progesterone induces a secretory protein in cultured rabbit endometrial stromal cells

Secretion of newly synthesized proteins by rabbit endometrial stromal cells in culture was studied. Progesterone (P) stimulated the synthesis and secretion of a protein with a mol. wt of approx 62 K and a pI of 6.5-7.0. Induction of 62 K protein synthesis was dose dependent; addition of 10 nM P to primary cultures caused a 2-fold or greater increase in the amount of this protein in the medium while addition of 1 microM P resulted in a 4.3-fold increase. Synthesis of this 62 K protein was not induced by estradiol, dexamethasone, or testosterone, nor was progesterone stimulation of the protein modified by estradiol. Thus, induction appears to be specific for a progesterone receptor mediated effect. Synthesis and secretion of this protein in the culture system described is potentially useful as a progestin bioassay.     

Design of a series of bicyclic HIV-1 integrase inhibitors. Part 2: Azoles: Effective metal chelators

Synthesis of a diverse set of azoles and their utilizations as an amide isostere in the design of HIV integrase inhibitors is described. The Letter identified thiazole, oxazole, and imidazole as the most promising heterocycles. Initial SAR studies indicated that these novel series of integrase inhibitors are amenable to lead optimization. Several compounds with low nanomolar inhibitory potency are reported.     

Strategies for the modulation of phase II metabolism in a series of PKCε inhibitors

Extensive phase II metabolism of an advanced PKCε inhibitor resulted in sub-optimal pharmacokinetics in rat marked by elevated clearance. Synthesis of the O-glucuronide metabolite as a standard was followed by three distinct strategies to specifically temper phase II metabolic degradation of the parent molecule. In this study, it was determined that the introduction of proximal polarity to the primary alcohol generally curbed O-glucuronidation and improved PK and physical chemical properties while maintaining potency against the target. Utilization of a Jacobsen hydrolytic kinetic resolution to obtain optically enriched final compounds is also discussed.     

Synthesis of Novel 3′-C-Hydroxymethyl Nucleosides by a Convergent Strategy

Abstract

Synthesis of 1-(2-deoxy-3-C-hydroxymethyl-α/β-D-elythro-pentofuranosyl)thymine and -cytosine by a convergent strategy using the precursors 7 and 8 have been accomplished.     

Computational-aided design of a library of lactams through a diversity-oriented synthesis strategy

Small molecule libraries for virtual screening are becoming a well-established tool for the identification of new hit compounds. As for experimental assays, the library quality, defined in terms of structural complexity and diversity, is crucial to increase the chance of a successful outcome in the screening campaign. In this context, Diversity-Oriented Synthesis has proven to be very effective, as the compounds generated are structurally complex and differ not only for the appendages, but also for the molecular scaffold. In this work, we automated the design of a library of lactams by applying a Diversity-Oriented Synthesis strategy called Build/Couple/Pair. We evaluated the novelty and diversity of these compounds by comparing them with lactam moieties contained in approved drugs, natural products, and bioactive compounds from ChEMBL. Finally, depending on their scaffold we classified them into β-, γ-, δ-, ε-, and isolated, fused, bridged and spirolactam groups and we assessed their drug-like and lead-like properties, thus providing the value of this novel in silico designed library for medicinal chemistry applications.     

Structure of the pentapeptide proctolin, a proposed neurotransmitter in insects.

Proctolin, a myotropic substance with potent activity on the proctodeal (hindgut) muscles of the cockroach, $\text{Periplaneta americana}$ (L.), has been identified by the use of Edman degradation and dansylation techniques as Arg-Tyr-Leu-Pro-Thr. Synthesis of the pentapeptide having this sequence and exhibiting the properties of natural proctolin confirmed the structure. Threshold activity on proctodeal muscle occurs at about 10⁻⁹ M proctolin.     

Biosemiotics,the Extended Synthesis,and Ecological Information: Making Sense of the Organism-Environment Relation at the Cognitive Level

This paper argues that the Extended Synthesis, ecological information, and biosemiotics are complementary approaches whose engagement will help us explain the organism-environment interaction at the cognitive level. The Extended Synthesis, through niche construction theory, can explain the organism-environment interaction at an evolutionary level because niche construction is a process guided by information. We believe that the best account that defines information at this level is the one offered by biosemiotics and, within all kinds of biosemiotic information available, we believe that ecological information (information for affordances) is the best candidate for making sense of the organism-environment relation at the cognitive level. This entanglement of biosemiotics, ecological information and the Extended Synthesis is promising for understanding the multidimensional character of the organism-environment reciprocity as well as the relation between evolution, cognition, and meaning.     

Nudol,a phenanthrene of the orchids Eulophia nuda, Eria carinata and Eria stricta

An amorphous phenanthrene, named nudol has been isolated from Eulophia nuda, Eria carinata and E. stricta. It was identified as 2,7-dihydroxy-3,4-dimethoxyphenanthrene. Synthesis of nudol and its dimethyl ether is described.     

Synthesis of a tetrasaccharide related to the repeating unit of the O-antigen from Escherichia coli K-12

Synthesis of a tetrasaccharide related to the repeating unit of the O-antigen from Escherichia coli K-12 is reported in the form of its octyl glycoside. Syntheses of the 1,2-cis glycosidic linkages have been accomplished by using NIS in conjunction with H₂SO₄-silica, and it was found to be stereoselective and productive. The synthesized tetrasaccharide will be utilized as the substrate for galactofuranosyltransferase, WbbI.     

Translational inhibition by heme of the synthesis of hepatic δ-aminolevulinate synthase in a cell-free system

Synthesis of δ-aminolevulinate synthase in a rabbit reticulocyte lysate system directed by total polysomes from the liver of allylisopropylacetamide-treated rats was studied with the combined use of [³H]leucine and a specific rabbit antibody. The protein synthesis observed in the cell-free system employed represented mainly the peptide chain elongation and its termination rather than the net synthesis involving initiation. Synthesis of δ-aminolevulinate synthase in this cell-free system was inhibited progressively with the increased addition of hemin; the synthesis was reduced to about 40% by about 30 μM hemin. Synthesis of total protein, however, was not significantly affected by the addition of hemin. The data obtained suggest that heme inhibits a peptide chain elongation step in the synthesis of δ-aminolevulinate synthase.     

Modification of a catalase by glutaraldehyde

Polycondensation of a catalase (EC 1.11.1.6) with glutaraldehyde in order to stabilize the quaternary structure of an enzyme, maintain its activity, and protect it from thermal denaturation was studied. Synthesis showed a superequivalent utilization of the aldehyde groups relative to the catalase amine groups, as a result of the formation of glutaraldehyde oligomers linked to the enzyme.     

Modification of a catalase by glutaraldehyde

Polycondensation of a catalase (EC 1.11.1.6) with glutaraldehyde in order to stabilize the quaternary structure of an enzyme, maintain its activity, and protect it from thermal denaturation was studied. Synthesis showed a superequivalent utilization of the aldehyde groups relative to the catalase amine groups, as a result of the formation of glutaraldehyde oligomers linked to the enzyme.