title: The pro-apoptotic action of new analogs of the insect gonadoinhibiting peptide Neb-colloostatin: synthesis and structure-activity studies.
abstract: Neb-colloostatin (SIVPLGLPVPIGPIVVGPR), an insect oostatic factor found in the ovaries of the flesh fly Neobellieria bullata, strongly induces apoptosis in insect haemocytes. To explain the role of Ser(1) and Pro(4) residues of Neb-colloostatin in the pro-apoptotic activity of this peptide, the synthesis of a series of analogs was performed, such as: [Ac-Ser(1)]- (1), [d-Ser(1)]- (2), [Thr(1)]- (3), [Asp(1)]- (4), [Glu(1)]- (5), [Gln(1)]- (6), [Ala(1)]- (7), [Val(1)]- (8), [d-Pro(4)]-(9), [Hyp(4)]- (10), [Acp(4)]- (11), [Ach(4)]- (12), [Ala(4)]- (13), [Ile(4)]- (14), and [Val(4)]-colloostatin (15). All peptides were bioassayed in vivo for the pro-apoptotic action on haemocytes of Tenebrio molitor. Additionally, the structural properties of Neb-colloostatin and its analogs were examined by the circular dichroism in water and methanol. Peptides 1, 4, 5, 7, 8, 10, 12, 14, and 15 strongly induce T. molitor haemocytes to undergo apoptosis and they show about 120-230% of the Neb-colloostatin activity at a dose of 1nM. The CD conformational studies show that the investigated peptides seem to prefer the unordered conformation.
authors.affiliation: Faculty of Chemistry, University of Wrocław, 14 F. Joliot-Curie Str., 50-383 Wrocław, Poland. mariola.kuczer@chem.uni.wroc.pl
authors.forename: Mariola
authors.initials: M
authors.lastname: Kuczer
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Czarniewska
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Rosiński
authors.forename: Marek
authors.initials: M
authors.lastname: Lisowski
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D006434:Hemocytes / Q000187:drug effects*; D006461:Hemolysis; D007301:Insect Hormones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D013712:Tenebrio / Q000166:cytology
chemical_list: D007301:Insect Hormones; C094892:Neb-colloostatin