Synthesis and biological evaluation of destruxin A and related analogs.
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.
Ast
T
T
Jerini Bio Tools GmbH, Berlin, Germany.
Barron
E
E
Kinne
L
L
Schmidt
M
M
Germeroth
L
L
Simmons
K
K
Wenschuh
H
H
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
D047630:Depsipeptides; D007306:Insecticides; D010456:Peptides, Cyclic; C040423:destruxin A