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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, 2010Computational Study on Helical Structure of α,α-DisubstitutedOligopeptides Containing Chiral α-Amino AcidsMasaaki Kurihara 1 , Yosuke Demizu 1 , Yukiko Sato 1 ,Nanako Yamagata 1 , Haruhiro Okuda 1 , Masanobu Nagano 2 ,Mitsunobu Doi 3 , Masakazu Tanaka 4 , and Hiroshi Suemune 21 Division of Organic Chemistry, National Institute of Health Sciences, Tokyo, 158-8501,Japan, 2 Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka,812-8582, Japan, 3 Osaka University of Pharmaceutical Sciences, Osaka, 569-1094,Japan, 4 Graduate School of Biomedical Sciences, Nagasaki University,Nagasaki, 852-8521, JapanIntroductionComputational simulation using conformational search calculations with AMBER* forcefield is most useful for conformational analysis of ligands in receptors or enzymes [1,2].Prediction of the conformation of oligopeptides using computational simulation presents aninteresting challenge to design of functionalized and bioactive peptides. We have shown theMonte Carlo conformational search method using MacroModel is useful to predict helicalstructures (α-helix, 3 10 -helix) of oligopeptides prepared from α α-disubstituted α-aminoacids. Moreover, we have studied conformational analysis of oligopeptides containingchiral α α-disubstituted α-amino acids to predict the helical screw sense of helicalstructures [3-9].Results and DiscussionWe calculated α,α-disubstituted peptides 1-6 (Figure 1) using MCMM conformationalsearch with various force fields (AMBER*, MMFF, OPLS) and showed the results inTable 1. These calculations were performed with MacroModel. In the case of usingAMBER* force field the results were in agreement with those of x-ray analysis and weremost stable conformation evaluated by 3-21G level molecular orbital calculation. Theseresults indicated that computational simulation using conformational search calculationswith AMBER* force field is most useful for conformational analysis of oligopeptidescontaining α,α-disubstituted α-amino acids.HCF 3 CO NONHOHN1ONHOHNCO2EtPhMeO OMe MeO OMe MeO OMe MeOOONHOHNMeOONHOHNOMe MeOONHOHNOMe MeO3ONHOMeOHNOMe MeOOOMeOMeHCF 3 CO NONHOHNONHOHNCO 2 EtPhOONHOMe OMe OMe OMeOHNONHOHNONHOHNONHOHNOOMe2OMe5OMeOMeOMeOH H H H H HHOHOHONNNNNNOEtOHOHOHOH H H H H HPhOMeO MeO MeO MeOONHOHNONHOHNONHOHNONHOHNOOMeMeO MeO MeO MeO46Fig. 1. Peptides 1-6.114