ABSTRACT
Original αγα tripeptides containing one ß,γ-diamino acid have been synthesized and their conformation determined by extensive NMR and molecular dynamic studies. These studies revealed the presence of a C(9) hydrogen bonded turn around the ß,γ-diamino acid which was stabilized by bulky side chains of the preceding residue. This turn can be considered as a mimic of the well-known γ-turn.
Subject(s)
Amino Acids, Diamino/chemistry , Oligopeptides/chemistry , Oligopeptides/chemical synthesis , Hydrogen Bonding , Models, Molecular , Nuclear Magnetic Resonance, Biomolecular , Protein ConformationABSTRACT
Small α/γ-peptides alternating α-aminoisobutyric acid and cyclic γ-amino acid residues are described. NMR studies together with restrained simulated annealing revealed that an extended backbone conformation largely dominates in solution for as short as 4-residues long oligomers. This new fold type is devoid of any hydrogen bond and characterized by a four-fold symmetry.
Subject(s)
Peptides/chemistry , Hydrogen Bonding , Nuclear Magnetic Resonance, Biomolecular , Protein Folding , Protein Structure, Tertiary , Solutions/chemistryABSTRACT
Over the past 20 years, the field of foldamers has rapidly increased. Many ß-peptides have already been described and shown interesting properties. γ-Peptides have more recently emerged but seem to be very interesting as well. In this review, we will cover every peptidomimetic oligomer that contains a γ-amino acid or an analogue and presents a structural feature. It includes γ-peptides but also hybrid α-γ peptides, ß-γ peptides and analogues such as oligoureas or aminoxy acids. We will present the biological properties of these oligomers.
Subject(s)
Peptides/chemistry , Peptidomimetics , Amino Acids/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Peptides/metabolism , Peptides/pharmacology , Protein ConformationABSTRACT
The synthesis of orthogonally protected diastereo- and enantiopure ß,γ-diamino acids starting from natural α-amino acids is described, as well as its application to the synthesis of fully protected 3-deoxyaminostatine.
Subject(s)
Amino Acids, Diamino/chemistry , Amino Acids, Diamino/chemical synthesis , Models, Molecular , Molecular Structure , Pyrrolidines/chemical synthesisABSTRACT
A general strategy for the amino acid homologation via Blaise reaction and subsequent reduction is presented. This strategy involves the preparation of protected alpha-amino nitriles from the corresponding amino acids, followed by the zinc-mediated condensation of tert-butyl bromoacetate, to give the imidazolidones after iminozincate cyclization. Reduction gave the saturated imidazolidinones with cis or trans stereochemistry, depending on the reduction conditions. This strategy was applied to nonfunctionalized amino acids and to functionalized amino acids such as serine and aspartic acid. Additionally, acidic hydrolysis of cis or trans imidazolidinones to the corresponding chiral 4-aminopyrrolidones is described.