title: Biaryl amino acid templates in place of D-Pro-L-Pro in cyclic beta-hairpin cationic antimicrobial peptidomimetics.
abstract: The turn-forming D-Pro-L-Pro template has been frequently used to promote regular beta-hairpin conformations in cyclic protein epitope mimetics. Here the use of three isomeric biaryl templates has been studied as alternatives to D-Pro-L-Pro in the preparation of beta-hairpin peptidomimetics. The o,o'- o,m'- and m,m'-isomers of carboxymethyl- and aminomethyl-substituted biaryl templates have been incorporated into novel macrocyclic mimics of the naturally occurring cationic antimicrobial peptide protegrin I. The presence of the o-carboxymethyl-o'-aminomethyl-biaryl template within the macrocyclic peptide resulted in the appearance of slowly interconverting atropisomers. Although none of the resulting mimetics adopted stable beta-hairpin structures in aqueous solution, they all nevertheless retained a significant antimicrobial activity against Gram positive and Gram negative bacteria. These mimetics provide interesting starting points for an optimization program in the search for potent and novel antimicrobial compounds.
authors: Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
authors: Nityakalyani
authors: N
authors: Srinivas
authors: Kerstin
authors: K
authors: Moehle
authors: Khaled
authors: K
authors: Abou-Hadeed
authors: Daniel
authors: D
authors: Obrecht
authors: John A
authors: JA
authors: Robinson
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D004151:Dipeptides / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D011487:Protein Conformation
chemical_list: D000596:Amino Acids; D023181:Antimicrobial Cationic Peptides; D004151:Dipeptides; D010456:Peptides, Cyclic; C448039:prolyl-proline