Cover image for Vol. 18 Issue 10

Editor: Meghan Campbell; Editorial Board Chairs: Thomas Carell, Donald Hilvert, Barbara Imperiali

Online ISSN: 1439-7633

Associated Title(s): ChemCatChem, ChemMedChem, ChemPhysChem, ChemSusChem

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May 04, 2017

Two recent VIP papers on mass spectrometry and mannosidase inhibitors

Very Important Paper: Mapping the Interactions of Selective Biochemical Probes of Antibody Conformation by Hydrogen--Deuterium Exchange Mass Spectrometry

Ulrike Leurs, Hermann Beck, Lea Bonnington, Ingo Lindner, Ewa Pol, Kasper Rand*

A major challenge during the development of therapeutic antibodies (IgG) is the assessment of changes to their higher-order structure. Now, K. Rand (University of Copenhagen, Denmark) and co-workers investigate the use of engineered Fab fragments, designed to bind to conserved regions of the IgG that are prone to undergo conformational changes. The selectivity of each probe to bind to distinct correctly folded parts of the IgG was identified by a combination of hydrogen--deuterium exchange mass spectrometry experiments (HDX-MS) and electron transfer dissociation (ETD). The use of these biochemical probes was also demonstrated in a surface plasmon resonance assay, which showed that their binding is sensitive to conformational changes occurring in IgG upon oxidation.

Very Important Paper: Selective Manipulation of Discrete Mannosidase Activities in the Endoplasmic Reticulum by Using Reciprocally Selective Inhibitors

Taiki Kuribara, Makoto Hirano, Gaetano Speciale, Spencer J. Williams, Yukishige Ito, Kiichiro Totani*

Around one third of N-linked glycoproteins produced in the cell fail to properly fold and must be detected and appropriately disposed of. Yet, the precise details of which glycan structures encode secretion and degradation signals are obscure. K. Totani (Seikei University, Japan) and co-workers report that known glycosidase inhibitors (deoxynojirimycin and deoxymannojirimycin) can selectively inhibit glycan-editing mannosidases provided their concentrations are carefully controlled. Using inhibitors to control the processing of a synthetic N-glycan in an ER-fraction, two discrete glycan processing pathways leading to secretion and degradation were discovered. This work provides fundamental insights into the signals that control the fate of glycoproteins.

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Recently Published Articles

  1. Sequence-Specific Covalent Capture Coupled with High-Contrast Nanopore Detection of a Disease-Derived Nucleic Acid Sequence

    Maryam Imani Nejad, Ruicheng Shi, Xinyue Zhang, Li-Qun Gu and Prof. Kent S. Gates

    Version of Record online: 26 MAY 2017 | DOI: 10.1002/cbic.201700204

    Thumbnail image of graphical abstract

    Reaching out and grabbing hold of specificity: Interstrand crosslinking chemistry can be used for highly selective covalent anchoring of a probe to a specific nucleic acid target sequence. We developed a new crosslinking reaction that uses probes prepared in a one-step procedure from inexpensive commercial reagents to achieve excellent sequence specificity under isothermal assay conditions.

  2. A tough nut to crack: Intracellular detection and quantification of heme in malaria parasites by a genetically encoded protein sensor

    Diana Imhof and Amelie Wißbrock

    Accepted manuscript online: 26 MAY 2017 03:20AM EST | DOI: 10.1002/cbic.201700274

  3. Next generation nucleic acid aptamers with two base modified nucleotides improve the binding affinity and potency

    Rakesh Naduvile Veedu and Hadi AlShamaileh

    Accepted manuscript online: 24 MAY 2017 09:20PM EST | DOI: 10.1002/cbic.201700276

  4. Exploring and Exploiting Acceptor Preferences of the Human Polysialyltransferases as a Basis for an Inhibitor Screen

    Jörg Ehrit, Dr. Timothy G. Keys, Mark Sutherland, Saskia Wolf, Chris Meier, Dr. Robert A. Falconer and Prof. Dr. Rita Gerardy-Schahn

    Version of Record online: 24 MAY 2017 | DOI: 10.1002/cbic.201700157

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    Two polysialyltransferases (polySTs; ST8SiaII and -IV) control polysialylation in humans, but ST8SiaII is predominant in tumours. Here we exploited differences in the preference for priming polysialic acid to develop a fluorescence assay in which polySTs can be differentiated in inhibitor screens. We describe CMP-Neu5Cyclo as a first competitive polyST inhibitor.

  5. Cyclotides: Overview and Biotechnological Applications

    Dr. Andrew Gould and Prof. Dr. Julio A. Camarero

    Version of Record online: 24 MAY 2017 | DOI: 10.1002/cbic.201700153

    Thumbnail image of graphical abstract

    Tied in knots: Cyclotides are globular microproteins with a unique head-to-tail cyclized backbone, stabilized by three disulfide bonds forming a cystine knot. The present review provides an overview on cyclotides and their applications as molecular imaging agents and peptide-based therapeutics.