We appreciate the invaluable contributions of the following reviewers during the editing of Vol. 8 Nos. 1–2.

Acknowledgments

We appreciate the invaluable contributions of the following reviewers during the editing of Vol. 8 Nos. 1–2.     

Studies on the koenigs-knorr reaction : Part V. Synthesis of 2-acetamido-2-deoxy-3-O-α-L-fucopyranosyl-α-D-glucose

Optically pure 2-acetamido-2-deoxy-3-O-α-L-fucopyranosyl-α-D-glucose was synthesized by the Koenigs-Knorr reaction of 2-O-benzyl-3,4-di-O-p-nitrobenzoyl-α-L-fucopyranosyl bromide with benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-α-D-glucopyrainoside. Reaction of 2,3,4-tri-O-acetyl-α-L-fucopyranosyl bromide gave the β-L-fucopyranosyl anomer. In contrast to the stereospecificity shown in this reaction by these two bromides, 2,3,4-tri-O-benzyl-α-L-fucopyranosyl bromide afforded a mixture of α-L and β-L anomers in almost equimolar proportions. The disaccharides synthesized were crystallized and characterized, and their optical purity demonstrated by g.l.c. of the per(trimethylsilyl) ethers of the corresponding alditols.     

Ester Derivatives of Nucleoside Inhibitors of Reverse Transcriptase: 2. Molecular Systems for the Combined Therapy with 3′-Azido-3′-Deoxythymidine and 2′,3′-Didehydro-3′-Deoxythymidine

The methods of synthesis of conjugates of anti-HIV nucleosides with various compounds, such as protease inhibitors, peptides, polysaccharides, and bicyclames are considered; they are designated for the combined therapy of HIV.     

Innatism in the Anthropology of A. L. Kroeber: A Critique of ‘the Boasian Paradigm’

Basing his analysis on Kroeber's ‘The superorganic’ (1917 Kroeber, A. L. 1917. The superorganic.. American Anthropologist, 19: 163–213. [Crossref] [Google Scholar]) and ‘Eighteen professions’ (1915 Kroeber, A. L. 1915. Eighteen professions.. American Anthropologist, 17: 283–88. [Crossref] [Google Scholar]), Derek Freeman has put forward the notion of a ‘Boasian paradigm’, whereby Kroeber is alleged to have perpetuated the biology/culture split suggested by Boas. I argue, instead, that there is a strong innatist element in Kroeber's writings throughout his long career; and that the articles noted above need to be placed in the social and intellectual contexts of their time, particularly the encroachment of the eugenics movement on social theory and its application to immigration restriction.     

Monte Carlo simulation of the α-amylolysis of amylopectin potato starch. 2. α-amylolysis of amylopectin

A model is presented that describes all the saccharides that are produced during the hydrolysis of starch by an -amylase. Potato amylopectin, the substrate of the hydrolysis reaction, was modeled in a computer matrix. The four different subsite maps presented in literature for -amylase originating from Bacillus amyloliquefaciens were used to describe the hydrolysis reaction in a Monte Carlo simulation. The saccharide composition predicted by the model was evaluated with experimental values. Overall, the model predictions were acceptable, but no single subsite map gave the best predictions for all saccharides produced. The influence of an (16) linkage on the rate of hydrolysis of nearby (14) linkages by the -amylase was evaluated using various inhibition constants. For all the subsites considered the use of inhibition constants led to an improvement in the predictions (a decrease of residual sum of squares), indicating the validity of inhibition constants as such. As without inhibition constants, no single subsite map gave the best fit for all saccharides. The possibility of generating a hypothetical subsite map by fitting was therefore investigated. With a genetic algorithm it was possible to construct hypothetical subsite maps (with inhibition constants) that gave further improvements in the average prediction for all saccharides. The advantage of this type of modeling over a regular fit is the additional information about all the saccharides produced during hydrolysis, including the ones that are difficult to measure experimentally.     

Enzymic Synthesis of Indole-3-Acetyl-1-O-β-d-Glucose : II. Metabolic Characteristics of the Enzyme

The first enzyme-catalyzed reaction leading from indole-3-acetic acid (IAA) to the myo-inositol esters of IAA is the synthesis of indole-3-acetyl-1-O-β-d-glucose from uridine-5′-diphosphoglucose (UDPG) and IAA. The reaction is catalyzed by the enzyme, UDPG-indol-3-ylacetyl glucosyl transferase (IAA-glucose-synthase). This work reports methods for the assay of the enzyme and for the extraction and partial purification of the enzyme from kernels of Zea mays sweet corn. The enzyme has an apparent molecular weight of 46,500 an isoelectric point of 5.5, and its pH optimum lies between 7.3 and 7.6. The enzyme is stable to storage at zero degrees but loses activity during column chromatographic procedures which can be restored only fractionally by addition of column eluates. The data suggest either multiple unknown cofactors or conformational changes leading to activity loss.     

Transfer of seabed mining technology: A stumbling block to U.S. ratification of the law of the sea convention?

Abstract

The Law of the Sea Convention's provisionson the transfer of seabed technology are designed to translate into specific terms the general notions (adopted in the U. N.’s Declaration of Principles of 1970) that the resources of the seabed are the “common heritage”; of humankind and that the developing nations are to gain special benefits from the exploitation of these resources. Some developed nations—in particular, the United States—have argued that these provisions are unfair, because they deprive the multinational enterprises of the developed world of the competitive advantage they have gained from their substantial investment in research and development and their innovative capabilities.

The transfer of technology is not a new concept. It is a mechanism that has been used systematically by many developing countries to ensure that foreign investments will produce a lasting infrastructure for continued national development. Multinational enterprises have learned to accommodate national needs in this area, and technology‐transfer requirements for land‐based investments have not deterred investments in the developing world.

The technology‐transfer provisions in the Law of the Sea Convention are ambiguous in certain respects, but the Preparatory Conference should provide ample opportunity to clarify these ambiguities and thus to accommodate the needs of both the investors and the developing nations. If this issue is examined from a common‐sense perspective, it should not continue to be a stumbling block that would prevent the United States from ratifying this important Convention.     

Nucleosides and Nucleotides. 232. Synthesis of 2′-C-Methyl-4′-thiocytidine: Unexpected Anomerization of the 2′-Keto-4′-thionucleoside Precursor

The synthesis of 2′-C-methyl-4′-thiocytidine (16) is described. Since the 2′-keto-4′-thiocytidine derivative 2β unexpectedly isomerized to 2α and the methylation of 2β proceeded predominantly from the less hindered α-face to give 7, the desired product 16 was synthesized via the Pummerer reaction of the sulfoxide 14 and N ⁴ -benzoylcytosine.     

New distinct compartments in the G2 phase of the cell cycle defined by the levels of γH2AX.

Induction of DNA double strand breaks leads to phosphorylation and focus-formation of H2AX. However, foci of phosphorylated H2AX (γH2AX) appear during DNA replication also in the absence of exogenously applied injury. We measured the amount and the number of foci of γH2AX in different phases of the cell cycle by flow cytometry, sorting and microscopy in 4 malignant B-lymphocyte cell lines. There were no detectable γH2AX and no γH2AX-foci in G₁ cells in exponentially growing cells and cells treated with PARP inhibitor (PARPi) for 24 h to create damage and reduce DNA repair. The amount of γH2AX increased immediately upon S phase entry, and about 10 and 30 γH2AX foci were found in mid-S phase control and PARPi-treated cells, respectively. The γH2AX-labeled damage caused by DNA replication was not fully repaired before entry into G₂. Intriguingly, G₂ cells populated a continuous distribution of γH2AX levels, from cells with a high content of γH2AX and the same number of foci as S phase cells (termed “G₂H” compartment), to cells that there were almost negative and had about 2 foci (termed “G₂L” compartment). EdU-labeling of S phase cells revealed that G₂H was directly populated from S phase, while G₂L was populated from G₂H, but in control cells also directly from S phase. The length of G₂H in particular increased after PARPi treatment, compatible with longer DNA-repair times. Our results show that cells repair replication-induced damage in G₂H, and enter mitosis after a 2–3 h delay in G₂L.     

Synthesis of heteroaromatic N-β-glycosides of N-acetylglucosamine under the conditions of phase transfer catalysis: I. Glucosaminides of 2-oxobenzazoles

Glycosylation of benzothiazolone-2, 5-methylbenzoxazolone-2, and benzothiazolone-2 with the full acetate of α-D-glucosaminyl chloride in the phase transfer systems investigated (solid-organic solvent and aqueous alkali-organic solvent) regioselectively leads to the corresponding N-β-D-glucosaminides, which is proved by ¹H NMR spectroscopy and X-ray analysis.     

Geometry of the dry-state oligomerization of 2′,3′-cyclic phosphates

Summary Evaporation of a solution of thymidine plus either theexo or theendo diastereomer of uridine cyclic 2,3-O, O-phosphorothioate (U > p(S) in 1,2-diaminoethane hydrochloride buffer gave the 2,5 and 3,5 isomers of (P-thio) uridylylthymidine (Up(S)dT) in a ratio of 1:2 with a combined yield of about 20%. These isomers were re-converted to U > p(S) and dT by a reaction that is known to proceed by an in-line mechanism. Both the 2,5 and 3,5 isomers gave as product the same diastereomer of U > p(S) that had been used originally in their formation. These dry-state prebiotic reactions (Verlander, Lohrmann, and Orgel 1973) are thus shown to be stereospecific, and both the 2,5 and 3,5 internucleotide bonds are formed by an in-line mechanism.Abbreviations DAE 1,2-diaminoethane - HPLC high pressure liquid chromatography - RNase bovine pancreatic ribonuclease A, EC 3.1.4.22 - TEAB triethylammonium bicarbonate - tris tris(hydroxymethyl)aminomethane - UMP(S) uridine monophosphorothioate - U > p uridine cyclic 2,3-phosphate - U > p(S) uridine cyclic 2,3-O, O-phosphorothioate - Up(S)dT (P-thio)uridylylthymidine - U2p(R_p-S)5dT (P-thio)uridylylthymidine with theR configuration at phosphorous, and a 2,5 internucleotide linkage     

Acyclic Nucleoside Analogues: III. A Synthesis of New 2′,3′-Dideoxy-2′,3′-Didehydronucleoside Analogues

The coupling of 5-acetoxy-1,1-dimethoxypent-2-ene with cytosine and thymine trimethylsilyl derivatives, as well as the reaction of 5-acetoxy-1-bromopent-2-ene with adenine sodium salt, yielded acyclic analogues of the corresponding nucleosides containing 5-acetoxy groups. They were deprotected with a saturated methanolic solution of ammonia to the target analogues of nucleosides, which were characterized with ¹H NMR, IR, and UV spectra.     

Crystal Structure of the LG1-3 Region of the Laminin ��2 Chain

Laminins are large heterotrimeric glycoproteins with many essential functions in basement membrane assembly and function. Cell adhesion to laminins is mediated by a tandem of five laminin G-like (LG) domains at the C terminus of the α chain. Integrin binding requires an intact LG1-3 region, as well as contributions from the coiled coil formed by the α, β, and γ chains. We have determined the crystal structure at 2.8-Å resolution of the LG1-3 region of the laminin α2 chain (α2LG1-3). The three LG domains adopt typical β-sandwich folds, with canonical calcium binding sites in LG1 and LG2. LG2 and LG3 interact through a substantial interface, but LG1 is completely dissociated from the LG2-3 pair. We suggest that the missing γ chain tail may be required to stabilize the interaction between LG1 and LG2-3 in the biologically active conformation. A global analysis of N-linked glycosylation sites shows that the β-sandwich faces of LG1 are free of carbohydrate modifications in all five laminin α chains, suggesting that these surfaces may harbor the integrin binding site. The α2LG1-3 structure provides the first atomic view of the integrin binding region of laminins.The laminins constitute a major class of cell-adhesive glycoproteins that are intimately involved in basement membrane assembly and function. Their essential roles in embryo development and tissue function have been demonstrated by numerous genetic studies and the analysis of severe human diseases resulting from mutations in laminin genes (1–4). All laminins are heterotrimers composed of three different gene products, termed α, β, and γ chains. At present, 16 mouse and human laminins are known, assembled from five α, three β, and three γ chains. The different laminins have characteristic expression patterns and functions in the embryo and adult animal (1). Laminins are cross-shaped molecules: the three short arms are composed of one chain each, while the long arm is a coiled coil of all three chains, terminating in a tandem of five laminin G-like (LG)² domains, LG1-5, contributed by the α chain (2). Basement membrane assembly requires polymerization via the short arms and cell attachment via the LG1-5 region (5, 6).Cell adhesion to laminins is mediated by multiple receptors: integrins bind to the LG1-3 region, whereas α-dystroglycan, heparan sulfate proteoglycans, and sulfated glycolipids bind predominantly to sites in the LG4-5 pair (7). Integrins are heterodimers with a large extracellular domain consisting of one α and one β chain, which both span the cell membrane and engage in transmembrane signaling (8). Of the 24 mouse and human integrins, the major laminin binding integrins are α3β1, α6β1, α7β1, and α6β4, which have distinct affinities for the different laminin isoforms (9). Although some studies have reported integrin binding or integrin-mediated cell adhesion to isolated LG domains or tandems (10–12), there is strong evidence to suggest that the coiled coil region and an intact γ chain tail are required for full integrin binding to the laminin LG1-3 region (13–18). Compared with integrin binding to collagen and fibronectin, which is understood in atomic detail (19, 20), the laminin-integrin interaction remains poorly characterized in structural terms. We previously determined crystal structures of the LG4-5 region of the laminin α1 and α2 chains and defined their receptor binding sites (21–23). Here, we report the crystal structure of the remainder of the laminin α2 receptor binding region, LG1-3.     

Nucleosides. 131. The Synthesis of 5-(2-Chloro-2-Deoxy-β-D-arabino-Furanosyl)Uracil. Reinterpretation of Reaction of ψ-Uridine With α-Acetoxyisobutyryl Chloride. Studies Directed Toward the Synthesis of 2′-Deoxy-2′-Substituted Arabino-Nucleosides. 2

Abstract

Treatment of ψ-uridine (3) with α-acetoxyisobutyryl chloride in acetonitrile gave, after deprotection, a mixture of four products: 5-(2-chloro-2-deoxy-β-D-arabinofuranosyl)uracil (10a), its 3′-chloro xylo isomer (11a), 2′-chloro-2′-deoxy-ψ-uridine (9a) and 4,2′-anhydro-ψ-uridine (8a). Each component was isolated by column chromatography. Compound 9 was converted to the known 1,3-dimethyl derivative 2 by treatment with DMF-dimethylacetal. Treatment of 10 and 11 with NaOMe/MeOH afforded the same 4,2′-anhydro-C-nucleoside 8. The 1,3-dimethyl analogues of 10 and 11, however, were converted to 2′,3′-anhydro-1,3-dimethyl-ψ-uridine (13) upon base treatment. The epoxide 13 was also prepared in good yield by treatment of 10 and 11 with DMF-dimethylacetal.