title: Solution state conformational preferences of dipeptides derived from N-aminoazetidinecarboxylic acid: an assessment of the hydrazino turn.
abstract: Four model compounds and four dipeptides containing N-aminoazetidinecarboxylic acid (AAzC) and a particular stereoisomer of 2-aminocyclobutanecarboxylic acid (ACBC) were studied to establish their solution state conformational preferences, particularly regarding the ability of AAzC to induce a three-center hydrogen-bonded folding feature known as a "hydrazino turn". On the basis of IR and NMR experiments, supported by molecular modeling, the AAzC residue adopted a trans configuration amenable to the formation of a cyclic eight-membered hydrogen bond conformation in solution, in all cases studied. The implication of the heterocyclic nitrogen atom of AAzC in the trans-like structure was demonstrated via a refined (1)H-(15)N HMBC experiment giving exploitable data at natural (15)N isotopic abundance, providing unprecedented evidence for the solution state hydrazino turn conformation. The predominance of this secondary structural feature depended on the configuration of the neighboring ACBC residue in the dipeptides: while the trans-ACBC derivatives prefer the hydrazino turn, the cis-ACBC derivatives may also populate low-energy 10-membered hydrogen-bonded ring structures. X-ray diffraction analysis of three compounds confirmed the presence of a solid state hydrazino turn in two cases, with geometries similar to those deduced from the solution state studies, but in the third compound, no intramolecular hydrogen-bonding feature was in evidence.
authors.affiliation: Laboratoire de Synthèse Organique et Méthodologie, ICMMO (UMR CNRS 8182), Université Paris Sud, 15 Rue Georges Clemenceau, 91405 Orsay cedex, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Altmayer-Henzien
authors.forename: Valérie
authors.initials: V
authors.lastname: Declerck
authors.forename: Denis
authors.initials: D
authors.lastname: Merlet
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Baltaze
authors.forename: Jonathan
authors.initials: J
authors.lastname: Farjon
authors.forename: Régis
authors.initials: R
authors.lastname: Guillot
authors.forename: David J
authors.initials: DJ
authors.lastname: Aitken
mesh_terms: D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003503:Cyclobutanes / Q000737:chemistry*; D004151:Dipeptides / Q000138:chemical synthesis*; D006834:Hydrazines / Q000737:chemistry*; D006860:Hydrogen Bonding; D008956:Models, Chemical; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D012996:Solutions; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: C542744:2-aminocyclobutanecarboxylic acid; D002264:Carboxylic Acids; D003503:Cyclobutanes; D004151:Dipeptides; D006834:Hydrazines; D012996:Solutions; D001383:Azetidinecarboxylic Acid