Structural specificity of beta-endorphin C-terminal tetrapeptide (MPF) in promoting urodele limb regeneration.
The ability of B-endorphin to initiate limb regeneration in hypophysectomised newts is confined to the human species of the peptide and is contained in its C-terminal tetrapeptide sequence, Lys-Lys-Gly-Glu (MPF). Results with fifteen MPF analogs show that: (a) small structural change at the C-terminal Glu residue destroys activity, (b) at the Gly position, change of -NH-CH2-CO by -NH-NH-CO- (Azgly) or -NH-CHMe-CO- (Ala) also destroys the activity, but methylation of the NH results in an analog (Sar) with good activity, (c) analogs in which the Lys residues are replaced by D-Lys, Nle or Orn may retain some activity, particularly when the second Lys is replaced by D-Lys, and (d) the activity is retained or increased by N-terminal acylation. By combining 'favourable' changes, an analog acetyl-Lys-D-Lys-Sar-Glu was devised which was 1.25 times more potent than MPF, and metabolically more stable.
Morley
J S
JS
Department of Neurological Sciences, University of Liverpool.
Ensor
D M
DM
D000595:Amino Acid Sequence; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005121:Extremities / Q000502:physiology*; D007016:Hypophysectomy; D007274:Injections, Intraperitoneal; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D010907:Pituitary Hormones / Q000008:administration & dosage; D012038:Regeneration / Q000187:drug effects*; D012455:Salamandridae; D001615:beta-Endorphin / Q000494:pharmacology*
D009842:Oligopeptides; D010907:Pituitary Hormones; D001615:beta-Endorphin