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Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010OH 3 COHO NH HOOHOCH 3Fig. 1. B. antharacis specificmonossacharide anthrose.Peptide Based Artificial Receptors forCarbohydrate RecognitionPredrag Cudic 1 , Andreja Jakas 2 , Nina Bionda 1 , and Maré Cudic 11 Torrey Pine Institute for Molecular Studies, Port St. Lucie, 34987, FL, U.S.A.; 2 Divisionof Organic Chemistry and Biochemistry, Rudjer Boskovic Institute, Zagreb, 10000, CroatiaIntroductionBacillus anthracis is a Gram-positive, rod-shaped, aerobic soil bacterium that causesanthrax in humans and other mammals. Recently it was found that one of the componentsof B. anthracis exosporium is a glycoprotein called BclA (Bacillus collagen-like protein ofanthracis) whose carbohydrate portion is composed of tetrasaccharide -Ant(1 3) -L-Rhap(1 3) -L-Rhap(1 2)L-Rhap [1]. The upstream terminal residue of thistetrasaccharide is a highly specific monosaccharide, named anthrose (4,6-dideoxy-4-[(3-hydroxy-3-methyl-1-oxobutyl)amino]-2-O-methyl-D-glucopyranose (Figure 1). Importantly,anthrose was not found in spores of eitherBacillus cereus or Bacillus thuringiensis, two speciesthat are the most phylogenetically similar toB. anthracis. Therefore, anthrose represents apromising target for the development of B. anthracisspecific detection agents.Carbohydrate binding protein mimicking moleculesusing the peptide based systems represent anattractive approach for the development of artificialreceptors for specific carbohydrate binding. These receptors should possess the necessarythree-dimensional structure, limited flexibility and lipophilic binding pocket where bindingcan occur through a combination of hydrophobic interaction and hydrogen bonds betweenreceptor molecules and carbohydrate substrates.Results and DiscussionAs a model system for artificial receptors we have chosen a cyclic cationic decapeptideantibiotic polymyxin B, which is known to bind the lipid A moiety of LPS with a highaffinity. Using a combinatorial chemistry approach we have prepared a soluble library ofOONHOOORink Amide MBHAresinNH-Fmoc1) 20% Piperidine/DMF2) Fmoc-AA, HOBt, HBTU,NMM, DMFOONHONHOHNORNHNH-MttHNO HONNR O HONH-BocHNORNH-Fmoc1) PdP(Ph 3) 4,CHCl 3, AcOH, NMP2) 20% Piperidine/DMF3) PyBop, HOBt, NMM,DMFNHRHNOHNNHOOBoc-HNRO HNOOHNOHNNHRHNOONH-Mtt1) 2% hydrazine/DMFOO2)HO N N OHPyBop,NMM,DMFHNOH 2NRHNONHHNOOH 2NROHNO HNONHOHNNHRONNNHOTFA, TIS, CH 2Cl 2NHRHNONHHNOOBoc-HNROHNHNNHO HNONHORONNNHO1) 1% TFA, TIS,CH 2Cl 22) PyBop, NMM, DMFNHRHNOHNNHOOOBoc-HNRHNOOHNOHNNHRONNHOOOONH-Mtt1Fig. 2. Solid phase synthetic strategy.88