Octopus glycosides: multivalent molecular platforms for testing carbohydrate recognition and bacterial adhesion Thisbe K. Lindhorst ⇑ , Michael Dubber Otto Diels Institute of Organic Chemistry, Christiana Albertina University of Kiel, Otto-Hahn-Platz 3/4, 24118 Kiel, Germany article info Article history: Received 18 May 2014 Received in revised form 26 June 2014 Accepted 30 June 2014 Available online xxxx Keywords: Multivalency Oligo-mannosylation Octopus glycosides Glycoclusters Bacterial adhesion Anti-adhesion therapy abstract Multivalency of carbohydrate–protein interactions is critical for cell adhesion, including attachment of bacteria to their host cells. To investigate specific parameters of multivalency effects, a variety of multi- valent glycoconjugates has been designed according to different mimetic approaches. Some 15 years ago, carbohydrates were elaborated as multivalent scaffold molecules for the preparation of carbohydrate- centred ‘octopus glycosides’ as well as of other carbohydrate-centred glycoconjugates. The beginning of this research is reported from a historical perspective and a selection of interesting applications is highlighted. Ó 2014 Elsevier Ltd. All rights reserved. 1. Introduction Over many years, it has been our interest to investigate multi- valency effects in carbohydrate recognition, employing artificially designed multivalent glycomimetics in solution. 1 This work has been inspired by the importance of multivalency in carbohy- drate–protein interactions 2 on the one hand. On the other hand, it was driven by the motivation to access multivalent glycoconju- gates or branched oligosaccharides, respectively, much faster than it would be possible by the synthesis of natural oligosaccharide structures. Certainly, it has to be kept in mind that the properties of structural mimetics can be different from those of the natural material. But, carbohydrate mimetics allow systematic alteration of specific structural characteristics and features and thus, testing of carbohydrate mimetics can effectively supplement investiga- tions with natural glycoconjugates. In order to achieve multivalent glycomimetic architectures, we first used non-carbohydrate dendritic scaffold molecules for func- tionalization with carbohydrates to furnish, what we called ‘glyco- dendrimers’, 3 simultaneously with the research group of René Roy. 4 Concomitantly, we and others started testing such glycoden- drimers as inhibitors of bacterial adhesion, in particular of type 1 fimbriae-mediated adhesion of bacterial cells to surfaces (vide infra). 5–8 However, when we realized, that simple glycodendrimers were no especially potent inhibitors of bacterial adhesion per se, 5 we looked for alternative ways of carbohydrate clustering, assum- ing that the nature of the multivalent scaffold can be critical for affinity and the inhibitory potency of the corresponding multiva- lent glycoconjugates. This consideration has inspired the idea to use carbohydrates as multivalent scaffold molecules instead of, for example, PAMAM dendrimers. 9 2. A new type of carbohydrate clustering We published a first paper about using carbohydrates as multivalent scaffold, entitled ‘A new type of carbohydrate cluster- ing: synthesis of a pentavalent glycocluster based on a carbohy- drate core’. 10 Here, we started from simple allyl a-D-glucoside (1) which was carried on in a Williamson etherification to give the per-allylated glucoside 2, which can be regarded as first versatile carbohydrate scaffold (Scheme 1). Further functionalization of 2 could be easily achieved by multiple radical addition of thiols to the double bonds of the molecule. Thus, irradiation of the penta-allylated glucoside with cysteamine hydrochloride in MeOH gave the pentaamine 3, which was obtained in the form of its penta-hydrochloride. At the time, we referred to the latter reaction as to the ‘well- known photoaddition reaction of cysteamine hydrochloride to allyl groups’, 10 citing the work of Lee and Lee back in 1974. 11 Today, the addition of thiols such as cysteamine to double bonds is called the http://dx.doi.org/10.1016/j.carres.2014.06.032 0008-6215/Ó 2014 Elsevier Ltd. All rights reserved. ⇑ Corresponding author. Tel.: +49 431 880 2023; fax: +49 431 880 7410. E-mail address: tklind@oc.uni-kiel.de (T.K. Lindhorst). Carbohydrate Research xxx (2014) xxx–xxx Contents lists available at ScienceDirect Carbohydrate Research journal homepage: www.elsevier.com/locate/carres Please cite this article in press as: Lindhorst, T. K.; Dubber, M. Carbohydr. Res. (2014), http://dx.doi.org/10.1016/j.carres.2014.06.032