Graphical Abstract: ChemBioChem 7/2006

The cover picture shows the alignment of the two geometric isomers (E isomer in blue, Z in turquoise) of 2-(3-benzylidene)-3-oxo-2,3-dihydrobenzo[b]thiophene-7carboxylic acid methyl ester at the active site of rabbit 12/15-lipoxygenase. In the Z configuration, the benzoyl moiety conflicts with the side chain of the C-terminal I663, which normally ligates the catalytic non-heme iron. Light irradiation induces Z-to-E isomerization, which flips the benzoyl ring over towards I593, the side chain of which limits the depth of the substrate binding pocket. There are no steric constraints for binding of the E isomer. Further details can be found in the article by H. Kuhn et al. on p. 1089 ff.


-1016
Transforming Carbonic Anhydrase into Epoxide Synthase by Metal Exchange Enantioselective epoxidation of styrene was observed in the presence of manganese-containing carbonic anhydrase as catalyst. The probable oxygentransfer reagent is peroxymonocarbonate, which has a structural similarity with the hydrogenocarbonate substrate of the natural reaction. Styrene was chosen as the enzyme possesses a small hydrophobic cavity close to the active site. Does aglycone linker conformation matter? Both E-and Z-linked a-C-galactosylceramides have been prepared by application of the Julia-Lythgoe-Kocienski synthesis to a C-formylgalactose and sulfones derived from phytosphingosine. Assays of cytokine levels induced by GalCers in mice suggest that the E geometry better resembles the preferred conformations of the flexible, saturated C-glycoside and the O-glycoside when bound to the CD1d molecule of antigen-presenting cells.

-1027
Target-Assisted Selection of Galactosyltransferase Binders from Dynamic Combinatorial Libraries. An Unexpected Solution with Restricted Amounts of the Enzyme Fix and look: Dynamic combinatorial chemistry coupled to an irreversible transformation has been used to identify enzyme binders in a library directed towards an a-1,3-galactosyltransferase. Small amounts of the protein induce an accumulation of the nonbinding amine products such as A resulting from the reduction of the corresponding imine binders. The binding properties of the imines are best mimicked by amides such as B.

-1030
Thermostable Glycosynthases and Thioglycoligases Derived from Thermotoga maritima b-Glucuronidase By using active-site mutants of the Thermotoga maritima b-glucuronidase, glucuronic acid-containing glycosides and thioglycosides have been made in high yields. These enzymes have potential use in the chemoenzymatic synthesis of a range of glycoconjugates, such as glycosaminoglycans (X = OH, NAc, H), that contain b-linked glucuronic and galacturonic acids. Substrate activity screening was used to rapidly identify a novel and potent (k inact /K i = 59 000 m À1 s À1 ) nonpeptidic chymotrypsin inhibitor with M W < 500. The inhibitor is more potent than the best reported tetrapeptidyl phosphonate chymotrypsin inhibitor and demonstrated selectivity over a panel of other serine proteases, including the closely related enzyme cathepsin G.

-1047
Efficient Sequence-Specific Purification of Listeria innocua mRNA Species by Triplex Affinity Capture with Parallel Tail-Clamps A gripping tail. The formation of stable triplexes of parallel tail-clamps with mRNA molecules is shown under acidic and also under neutral and slightly basic pH conditions (see schematic representation). As an example of the fore-seen applications of this process, efficient and specific purification of Listeria innocua iap mRNA molecules was achieved from an L. innocua total RNA solution by triplex affinity capture.

-1077
Inactivation of gilGT, Encoding a C-Glycosyltransferase, and gilOIII, Encoding a P450 Enzyme, Allows the Details of the Late Biosynthetic Pathway to Gilvocarcin V to be Delineated Road map to gilvocarcin V. Two structural features that are crucial for the biological activity of antitumor antibiotic gilvocarcin V-its C8 vinyl group and C-glycosidically bound d-fucose residue-are shaped in late biosynthetic steps by the enzymes GilOIII and GilGT, respectively (see scheme). We demonstrate this by a series of experiments that include the analysis of mutant strains in which the gilOIII and gilGT genes were deleted.

-1088
On the Sequence of Bond Formation in Loline Alkaloid Biosynthesis Who's next? The order of bond-forming steps in the biosynthetic pathway to loline alkaloids was determined by feeding deuterated compounds to Neotyphodium uncinatum. Proline and homoserine combine to form N-(3-amino-3-carboxypropyl)proline, which is decarboxylated and cyclized to form 1-aminopyrrolizidine. The addition of an oxygen atom to 1-aminopyrrolizidine completes the biosynthesis. Scyllo-or myo-. Physicochemical studies with potentiometric and NMR titrations show that, at physiological PH, the microprotonation patterns of synthetic scyllo-inositol pentakisphosphate (scyllo-InsP 5 ) resemble those of its close relative, the intracellular signalling molecule myo-Ins(1,3,4,5,6)P 5 , as shown by their conditional probabilities (%) at pH 7.5. This makes scyllo-InsP 5 a promising tool for identifying those biological effects of myo-InsP 5 that are mediated by specific binding proteins (centre), rather than by nonspecific electrostatic effects.
Supporting information on the WWW (see article for access details).
* Author to whom correspondence should be addressed. ADDENDUM Shortly before the submission of our manuscript on microarrays of lipolytic enzymes to ChemBioChem in 2005, Dr. Funeriu and his colleagues published a study that described "Enzyme family-specific and activity-based screening of chemical libraries using enzyme microarrays". [1] The authors named this type of application "Thematic Enzyme Microarrays" (TEMA). In ref.

BOOKS
[8] on p. 532 of our publication, we wanted to emphasize that the same authors had already successfully applied hydrogel NHS slides in enzyme microarray technology before our laboratory used them for the preparation of lipase and esterase chips.  Members of the GDCh must place their orders directly at the publishers (via Subscription Service above).

Delivery:
By direct mail (printed matter) or through book-sellers. * Change of address: Please notify your bookseller or the publishers immediately. * Cancellation of subscriptions: The publishers must be notified not later than three months before the end of the calendar year.
Registered names, trademarks, etc., used in this journal, even when not marked as such, are not to be considered unprotected by law.
All rights reserved (including those of translation into foreign languages).
No part of this issue may be reproduced in any form-by photoprint, microfilm, or any other means-or transmitted or translated into a machine language without the express written consent of the publishers.
Responsibility: This journal was carefully produced in all its parts. Nevertheless, the authors, editor, and publisher do not warrant the information contained therein to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details, or other items may inadvertently be inaccurate.
Valid for users in the USA: The copyright owner agrees that copies of the articles may be made for personal or internal use, or for the personal or internal use of specific clients. This consent is given on the condition, however, that the copier pay the stated per-copy fee through the Copyright Clearance Center, Inc., for copying beyond that permitted by Authors who wish to publish in ChemBioChem should consult the current "Notice to Authors", which appears on the ChemBioChem homepage at http://www.chembiochem.org, before they draft their manuscript.