title: D-proline-based peptidomimetic inhibitors of anthrax lethal factor.
abstract: In this work we reported the generation of d-proline-derived hydroxamic acids as inhibitors of anthrax lethal factor (LF), taking advantage of a pyrrolidine ring as the central scaffold and a hydroxamate group as the Zn(2+) chelating agent. The introduction of two hydrophobic groups addressing the S1' subsite and a long substrate-binding groove was conceived by overlapping the bioactive conformations of two reported LF inhibitors. Micromolar affinity of compound 38 suggested cis-3-substituted-1-sulfonamido-d-proline hydroxamic acids as a promising class of peptidomimetic inhibitors for developing novel LF inhibitors.
authors.affiliation: Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 13, I-50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Calugi
authors.forename: Andrea
authors.initials: A
authors.lastname: Trabocchi
authors.forename: Claudia
authors.initials: C
authors.lastname: Lalli
authors.forename: Antonio
authors.initials: A
authors.lastname: Guarna
mesh_terms: D000942:Antigens, Bacterial; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors*; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D057786:Peptidomimetics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011392:Proline / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D006877:Hydroxamic Acids; D057786:Peptidomimetics; C030325:anthrax toxin; D011392:Proline