Protein epitope mimetics

Fasan, R., Dias, R.L.A., Moehle, K., Zerbe, O., Obrecht, D., Mittl, P.R.E., Grutter, M.G., and Robinson, JA. (2006) Structure-activity studies in a family of p-hairpin protein epitope mimetic inhibitors of the p53-HDM2 protein-protein interaction. ChemBioChem. 7, 515-526. 

Fasan R et al (2006) Structure-activity studies in a family of beta-hairpin protein epitope mimetic inhibitors of the p53-HDM2 protein-protein interaction. Chembiochem 7(3) 515—526... 

F., Moehle, K., and Obrecht, D. (2008) The design, structures and therapeutic potential of protein epitope mimetics. Drug Discovery Today, 13, 944-951. 

An important class of peptide-derived macrocycles mimicking an entire functional epitope are Protein Epitope Mimetics (PEMs) of the general formula 3 (Figure 8.3). PEM molecules are cyclopeptide-like molecules composed of a conformation-inducing template and a peptide chain of 4-20 amino acids, mimicking p-hairpin- and a-helical functional epitopes of proteins, the most important exposed protein epitopes involved in many... 

In Section II.C we will present novel tricyclic xanthene derived amino acid templates, which allow the construction of libraries of cyclic conformationally constrained peptide loop mimetics using the split-and-mix method without having to use tagging and deconvolution strategies. In Section III we will focus on parallel and combinatorial approaches devoted to the synthesis of small molecule, non-peptidic compound collections, which in addition offer the possibility to incorporate structural features derived from protein epitope mapping into conformationally constrained peptide mimetics. 

A similar approach was used in the synthesis of the sialyl Lewis X mimetics of type 85 (Scheme 13.22).66 Protein crystallization,67 conformational studies of sLex in solution68 and in bound form to E- and P-selectin69 as well as the study of structure-function relationships70,71 gave information about the functional groups of the sLex-epitope essential for the binding to the selectins. Synthesized mimetics must contain the three essential hydroxyl functions of the fucose. Sialic acid, galactose, and... 

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