The effect of N-terminal substitutions on the biological activity of MSH fragments

In order to study the role of N-terminal substitutions of peptide sequences related to the active site of α-melanotropin, Glp⁵]α-MSH(5–10), Glp⁵, -Phe⁷]α-MSH(5–10), Sar⁵, -Phe⁷]α-MSH(5–10), Nle⁴, -Phe⁷]α-MSH(4–10), N-carbamoyl]α-MSH(5–10), and formyl and acetyl derivatives of α-MSH(5–10), Gly⁵]α-MSH(5–10) and Gly⁵, -Phe⁷]α-MSH(5–10), were synthesized in solution. The N-terminal acylations enhance by 2 to 10 times the melanin-dispersing activity of the unsubstituted sequences. Alkylation of the N-terminus does not change the biological activity of the parent peptide, suggesting the necessity of a carbonyl group for increasing the hormonal effect.