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 Ser1 and Pro4 residues of Neb-colloostatin in the pro-apoptotic activity of this peptide, the synthesis of a series of analogs was performed, such as: [Ac-Ser1]- (1), [d-Ser1]- (2), [Thr1]- (3), [Asp1]- (4), [Glu1]- (5), [Gln1]- (6), [Ala1]- (7), [Val1]- (8), [d-Pro4]-(9), [Hyp4]- (10), [Acp4]- (11), [Ach4]- (12), [Ala4]- (13), [Ile4]- (14), and [Val4]-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.