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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, 2010Synthesis of Novel Peptides Containing Unusual γ-Amino acidsand Investigation of Their NanostructuresB. Talaei, A. Arabanian, and S. Balalaie*Peptide Chemistry Research Center, K. N. Toosi University of Technology,Tehran, P.O. Box 15875-4416, IranIntroductionIt was shown that insertion of an unusual amino acid in a peptide sequence could affect thesecondary structure and also their biological activities. Self-assembled protein and peptidenanostructures are envisioned to serve as important building blocks in futurenanotechnological devices and assemblies. Meanwhile, there are some reports about themechanism of amyloid fibril formation which led to the unexpected discovery thatdiphenylalanine, NH 2 -Phe-Phe-COOH, is core recognition motif of the Alzheimer’sβ-amyloid [1-2]. Investigations have shown that the Phe-Phe dipeptide rearranges due to theappropriate π-stacking interactions such that 6 species make a ring with a hydrophilic interiorand hydrophobic exterior [3]. Numerous experiments performed by Gazit, et al. haveinvestigated the effect of aromatic groups and the capabilities of the resulting molecule in therearrangement process by using homoaromatic compounds instead of phenylalanine [4] or byaddition of an aromatic species such as Fmoc to the F-F structure. They investigated the πinteractions and the formations of the associated nanostructures [5]. On the other hand, otherexperiments which added molecules such as PEG [6] or aliphatic compounds to the end of theamino acid side chains and achieved nanofibril or other structures, made us utilize aminoacids in our molecule which could induce more aliphatic properties to the phenylalaninephenylalaninemolecule. γ-Amino acids have important biological properties (as regulatorymolecules, intermediary metabolities, storage compounds, and defensive weapons). γ-Aminobutyric acid (GABA) is a major physiological inhibitor of neuro-transmission in thebrain [7]. Meanwhile, gabapentin, baclofen and other γ-amino acids are used for the treatmentof CNS diseases. According to these findings, we were encouraged to synthesize some novelpeptides which contained γ- amino acids such as baclofen and gabapentin in their backbones.Results and DiscussionDue to the existence of aromatic moiety in the structure of baclofen it was selected ascandidate for our investigation. Gabapentin’s structure has a non polar property due to acyclohexyl ring connected to its β-carbon atom. Dipeptide (F-F) was synthesized according tothe known solution phase peptide synthesis methodology, and additional unusual amino acidswere added to the peptide chain. By connecting these two unusual amino acids todi-phenylalanine, new analogues were synthesized which could play important roles in theformation of molecular assemblies due to π-stacking interactions. The di- tri- and tetrapeptideswere synthesized in solution phase and with consideration of orthogonality and usingof suitable protection and deprotection strategy.(a) (b) (c)Fig. 1. a) Gel formation for compound 15; b) SEM micrographs of the compounds 6 and8; c) Optimized structure of compound 9.578