Sawyer T K, Sanfilippo P J, Hruby V J, Engel M H, Heward C B, Burnett J B, Hadley M E
Proc Natl Acad Sci U S A. 1980 Oct;77(10):5754-8. doi: 10.1073/pnas.77.10.5754.
alpha-Melanocyte-stimulating hormone (alpha-MSH) reversibly darkens frog skins by stimulating melanosome movement (dispersion) within melanophores. Heat-alkali treatment of alpha-MSH results in prolonged biological activity of the hormone. Quantitative gas chromatographic analysis of the hydrolyzed heat-alkali-treated peptide revealed partial racemization particularly at the 4(methionine) and 7(phenylalanine) positions. [Nle4]-alpha-MSH, a synthetic analogue of alpha-MSH, reversibly darkens frog skins and also exhibits prolonged activity after heat-alkali treatment. Synthesis of [Nle4, D-Phe7]-alpha-MSH provided an analogue with prolonged biological activity identical to that observed with heat-alkali-treated alpha-MSH or [Nle4]-alpha-MSH. [Nle4, D-Phe7]-alpha-MSH was resistant to enzymatic degradation by serum enzymes. In addition, this peptide exhibited dramatically increased biological activity as determined by frog skin bioassay, activation of mouse melanoma adenylate cyclase, and stimulation of mouse melanoma cell tyrosinase activity. This Nle4, D-Phe7 synthetic analogue of alpha-MSH is a very porent melanotropin, 26 times as potent as alpha-MSH in the adenylate cyclase assay. The resistance of the peptide to enzymatic degradation and its extraordinarily potent and prolonged biological activity should make this analogue of alpha-MSH an important molecular probe for studying the melanotropin receptors of both normal and abnormal (melanoma) melanocytes.
α-黑素细胞刺激素（α-MSH）通过刺激黑素细胞内黑素小体的移动（分散）使蛙皮可逆性变黑。对α-MSH进行热碱处理可使该激素的生物活性延长。对经热碱处理后水解的肽进行定量气相色谱分析发现存在部分消旋化，尤其是在4（甲硫氨酸）和7（苯丙氨酸）位。[Nle4]-α-MSH是α-MSH的一种合成类似物，可使蛙皮可逆性变黑，并且在热碱处理后也表现出延长的活性。[Nle4, D-Phe7]-α-MSH的合成提供了一种具有与热碱处理的α-MSH或[Nle4]-α-MSH相同的延长生物活性的类似物。[Nle4, D-Phe7]-α-MSH对血清酶的酶促降解具有抗性。此外，通过蛙皮生物测定、小鼠黑素瘤腺苷酸环化酶的激活以及小鼠黑素瘤细胞酪氨酸酶活性的刺激来确定，该肽表现出显著增强的生物活性。这种α-MSH的Nle4, D-Phe7合成类似物是一种非常强效的促黑素，在腺苷酸环化酶测定中其效力是α-MSH的26倍。该肽对酶促降解的抗性及其极其强效和延长的生物活性应使这种α-MSH类似物成为研究正常和异常（黑素瘤）黑素细胞促黑素受体的重要分子探针。
