4-NORLEUCINE, 7-D-PHENYLALANINE-ALPHA-MELANOCYTE-STIMULATING HORMONE - A HIGHLY POTENT ALPHA-MELANOTROPIN WITH ULTRALONG BIOLOGICAL-ACTIVITY
4-NORLEUCINE, 7-D-PHENYLALANINE-ALPHA-MELANOCYTE-STIMULATING HORMONE - A HIGHLY POTENT ALPHA-MELANOTROPIN WITH ULTRALONG BIOLOGICAL-ACTIVITY
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DOI：
10.1073/pnas.77.10.5754
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发表时间：
1980-01-01
期刊：
影响因子：
--
通讯作者：
HADLEY, ME
中科院分区：
文献类型：
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作者：
SAWYER, TK;SANFILIPPO, PJ;HADLEY, ME
α-黑素细胞刺激素(α-MSH)通过刺激黑素小体在黑素基团内的运动(分散)，可逆地使青蛙皮肤变黑。α-MSH的热-碱处理导致色酮的生物活性延长。经热-碱处理的水解肽的定量气相色谱分析表明，在4(蛋氨酸)和7(苯丙氨酸)位发生了部分外消旋。[Nle4]-α-MSH，一种α-MSH的合成类似物，可逆地使青蛙皮肤变黑，并在热-碱处理后显示出更长的活性。[Nle4，D-Phe7]-α-MSH的合成提供了一种具有持久生物活性的类似物，与热碱处理的α-MSH或[Nle4]-α-MSH的观察结果相同。[Nle4，D-Phe7]-α-MSH耐血清酶降解。此外，通过蛙皮生物活性、小鼠[S-91]黑色素瘤腺苷环化酶的激活和对小鼠黑色素瘤细胞酪氨酸酶活性的刺激表明，该多肽具有显著的生物学活性。这种Nle4，D-Phe7合成的α-MSH类似物是一种非常有效的促黑激素，在腺苷环化酶试验中的效力是α-MSH的26倍。该肽对酶降解的抵抗力以及其非凡的强大和持久的生物学活性应该使这种α-MSH的类似物成为研究正常和异常(黑色素瘤)黑素细胞的促黑激素受体的重要分子探针。
.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 hromone. 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 analog 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 analog 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 [S-91] melanoma adenylate cyclase and stimulation of mouse melanoma cell tyrosinase activity. This Nle4,D-Phe7 synthetic analog of .alpha.-MSH is a very potent 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 analog of .alpha.-MSH an important molecular probe for studying the melonotropin receptors of both normal and abnormal (melanoma) melanocytes.