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Minimalist secondary structure mimics are typically made to resemble one interface in a protein-protein interaction (PPI), and thus perturb it. We recently proposed suitable chemotypes can be matched with interface regions directly, without regard for secondary structures. Here we describe a modular synthesis of a new chemotype 1, simulation of its solution-state conformational ensemble, and correlation of that with ideal secondary structures and real interface regions in PPIs. Scaffold 1 presents amino acid side-chains that are quite separated from each other, in orientations that closely resemble ideal sheet or helical structures, similar non-ideal structures at PPI interfaces, and regions of other PPI interfaces where the mimic conformation does not resemble any secondary structure. 68 different PPIs where conformations of 1 matched well were identified. A new method is also presented to determine the relevance of a minimalist mimic crystal structure to its solution conformations. Thus dld-1-faf crystallized in a conformation that is estimated to be 0.91 kcal-mol-1 above the minimum energy solution state. Do we know, when designing a new peptidomimetic scaffold like the one shown, how it can resemble secondary structures? Design and modular synthesis of this elongated mimic is reported, and the structure is related to ideal and real structures at PPI interfaces.

Sixteen and 24 membered aza-β3-peptidic macrocycles containing a α-hydrazinoacid or a β3-aminoacid were synthesized. The conformation of these pseudopeptides was determined by using NH chemical shift analysis, NH extinction, VT-NMR e

The present invention relates to a process for producing amino acid derivatives such as optically active β-amino acid in short steps with good yield and high optical purity, which comprises reacting a keto acid of the formula (1): wherein R1 is hydrogen, an optionally substituted hydrocarbon, etc.; R2 is a spacer; and R3 is an optionally substituted alkoxy, etc., or a salt thereof, with ammonia or an amine or a salt thereof in the presence of a chiral catalyst and in the presence or absence of an acid and/or a fluorine-containing alcohol, to give an amino acid derivative of the formula (2): wherein Q is a group formed by removing one hydrogen atom from ammonia or an amine; X' is an acid and/or a fluorine-containing alcohol; and b is 0 or 1.

β-Lactone electrophiles are subject to regioselective addition-elimination (AE) or SN2 ring opening with various nitrogen-based nucleophiles. Primary and secondary amines promote AE ring opening to deliver products that are the functional equiv

The β-hexapeptide (H-β-HVal-β-HAla-β-HLeu)2-OH (2) was prepared from the component L-β-amino acids by conventional peptide synthesis, including fragment coupling. A cyclo-β-tri- and a cyclo-β-hexapeptide were also prepared. The β-amino acids we