The active sequence in the acth molecule responsible for inhibition of the extinction of conditioned avoidance behaviour in rats

The effect of structural analogues of the N-terminal decapeptide of ACTH on inhibition of extinction of a conditioned avoidance response in rats has been studied. Studies involving the relation between chain length and behavioural activity revealed that the sequence 4–10 is the shortest peptide which affects the avoidance response as potently as does the decapeptide. Although the presence of the sequence 1–3 is not essential for the behavioural effect, slight structural modifications within these 3 amino acids are accompanied by loss of activity

Neuroleptic-like activity of peptides related to [DES-TYR1] γ-endorphin: Structure activity studies

The potency of various fragments of γ-endorphin (β-LPH61–77) was compared on their ability to facilitate extinction of pole-jumping avoidance behavior and their effects in two “grip tests” used as measures of neuroleptic-like activity. It appeared that β-LPH66–77 is the shortest sequence which shows potencies in the three tests comparable to that of DTγE (β-LPH62–77). The activity of β-LPH67–77 was less. It is proposed that β-LPH66–77 rather than DTγE represents an endogenous neuroleptic-like neuropeptide which may play a key role in psychopathology

Inhibition of [gamma]-endorphin generating endopeptidase activity of rat brain by peptides: Structure activity relationship

Gamma-Endorphin generating endopeptidase (gammaEGE) activity is an enzyme activity which converts beta-endorphin into gamma-endorphin and beta-endorphin-(18–31). The inhibitory potency on gammaEGE activity of neuropeptides and analogues or fragments of neuropeptides was tested. Dynorphin-(1–13) (IC50: 0.14 μM), human beta-endorphin-(1–31) (IC50: 15.5 μM), porcine ACTH-(1–39) (IC50: 6.3 μM), and substance P (IC50: 26 μM) had an inhibitory activity on gammaEGE activity. beta-Endorphin-(18–31) (IC50: 0.35 μM) but not gamma-endorphin potently inhibited gammaEGE activity. The IC50 of poly (Lys)40–60 was 0.8 μM. It is concluded that 1) gammaEGE activity is strongly inhibited by its product beta-endorphin-(18–31), 2) the enzyme is strongly inhibited by peptides with an aromatic amino acid at the NH2-terminal and/or basic amino acids in the COOH-terminal of the peptide chain