title: Synthesis and biological evaluation of destruxin A and related analogs.
abstract: This report describes the development of an efficient solid-phase synthesis protocol and adaptation of reported solution phase procedures for the synthesis of the cyclic depsihexapeptide destruxin A and related analogs. The solid-phase method described is based on standard Fmoc peptide chemistry, including a new synthetic method for the assembly of the depsi bond-containing unit. In order to select analogs of destruxin A for synthesis and evaluation of insecticidal activity, the work of Hellberg et al., describing a set of Z-descriptors for amino acid side-chains comparing their physicochemical properties, was utilized. Destruxin A and 27 different analogs with structural variations in four residues were synthesized and insecticidal activity was evaluated via injections into tobacco budworm (Heliothis virescens) larvae. Several destruxin A analogs were found to be at least as potent as the native compound.
authors.affiliation: Jerini Bio Tools GmbH, Berlin, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Ast
authors.forename: E
authors.initials: E
authors.lastname: Barron
authors.forename: L
authors.initials: L
authors.lastname: Kinne
authors.forename: M
authors.initials: M
authors.lastname: Schmidt
authors.forename: L
authors.initials: L
authors.lastname: Germeroth
authors.forename: K
authors.initials: K
authors.lastname: Simmons
authors.forename: H
authors.initials: H
authors.lastname: Wenschuh
mesh_terms: D000818:Animals; D001671:Biochemistry / Q000379:methods*; D047630:Depsipeptides; D004353:Drug Evaluation, Preclinical; D007306:Insecticides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009036:Moths / Q000187:drug effects; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D047630:Depsipeptides; D007306:Insecticides; D010456:Peptides, Cyclic; C040423:destruxin A