12 research outputs found
Review of the Palaearctic species of Ismaridae Thomson, 1858 (Hymenoptera: Diaprioidea)
This is an open access article, available to all readers online, published under a Creative Commons BY-NC-ND license: https://creativecommons.org/licenses/by-nc-nd/3.0/. The attached file is the published version of the article
Polymeric dibromomaleimides as extremely efficient disulfide bridging bioconjugation and pegylation agents
A series of dibromomaleimides have been shown to be very efficacious at insertion into peptidic disulfide bonds. This conjugation proceeds with a stoichiometric balance of reagents in buffered solutions in less than 15 min to give discrete products while maintaining the disulfide bridge and thus peptide conformation. The insertion is initiated by disulfide reduction using a water-soluble phosphine, tris(2-carboxyethyl)phosphine (TCEP) which allows for subsequent substitution of the two maleimide bromides by the generated thiols. Reaction of salmon calcitonin (sCT) with 2,3-dibromomaleimide (1.1 excess) in the presence of TCEP (1.1 equiv) in aqueous solution at pH 6.2 gives complete production of a single conjugate which requires no workup. A linear methoxy poly(ethylene glycol) (PEG) was functionalized via a Mitsunobu reaction and used for the successful site-specific and rapid pegylation of sCT. This reaction occurs in 15 min with a small stoichiometry excess of the pegylating agent to give insertion at the disulfide with HPLC showing a single product and MALDI-ToF confirming conjugation. Attempts to use the group in a functional ATRP polymerization initiator led to polymerization inhibition. Thus, in order to prepare a range of functional polymers an indirect route was chosen via both azide and aniline functional initiators which were converted to 2,3-dibromomaleimides via appropriate reactions. For example, the azide functional polymer was reacted via a Huisgen CuAAC click reaction to an alkyne functional 2,3-dibromomaleimide. This new reagent allowed for the synthesis of conjugates of sCT with comb polymers derived from PEG methacrylic monomers which in addition gave appropriate cloud points. This reaction represents a highly efficient polymer conjugation method which circumvents problems of purification which normally arise from having to use large excesses of the conjugate. In addition, the tertiary structure of the peptide is efficiently maintained
Sequential phosphine-catalyzed, nucleophilic thiol ene/radical-mediated thiol-yne reactions and the facile orthogonal synthesis of polyfunctional materials
The first example of highly efficient sequential thiol-ene/thiol-yne reactions conducted in an orthogonal manner is presented and its broad application in the synthesis of polyfunctional materials demonstrated. The anionic chain mechanism of the phosphine-mediated thiol-ene reaction is highlighted, as is the radical-mediated thiol-yne reaction. Kinetic data for a model reaction are presented, followed by a discussion of the synthesis of a range of materials with diverse functionality, including an example of potential biomedical significance. © 2009 American Chemical Society