A series of six ligands for the human formyl peptide receptor: tetrapeptides with high chemotactic potency and efficacy.
A series of six ligands for the human formyl peptide receptor: tetrapeptides with high chemotactic potency and efficacy.
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人类甲酰肽受体的一系列六种配体：具有高趋化效力和功效的四肽。
DOI：
10.1073/pnas.84.22.7967
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发表时间：
1987
影响因子：
11.1
通讯作者：
Leonard,EJ
中科院分区：
文献类型：
--
作者：
Rot,A;Henderson,LE;Copeland,TD;Leonard,EJ
我们最近从金黄色葡萄球菌的培养液中分离出一种趋化肽，它含有等摩尔量的蛋氨酸、亮氨酸、苯丙氨酸和异亮氨酸。它与人白细胞的甲酰甲硫氨酰肽受体相互作用，并且具有比广泛研究的三肽激动剂fMet-Leu-Phe高得多的效力和功效。假设引诱剂是甲酰甲硫氨酰四肽，我们合成了六种可能的序列，并测试了产物的趋化效力和功效，以及它们抑制荧光素异硫氰酸酯标记的fMet-Leu-Phe-Lys与人单核细胞结合的能力。通过六种肽抑制荧光素标记的fMet-Leu-Phe-Lys结合所需的浓度涵盖三个数量级。趋化效力（引起50%最大趋化反应的浓度）范围为3.1 × 10（-11）M至6.4 × 10（-10）M;效力（在最佳引诱剂浓度下迁移的单核细胞百分比）范围为41%至66%。当对六种合成四肽的趋化效力进行排序时，它们根据苯丙氨酸的位置配对。对于在位置3具有苯丙氨酸的两种肽，平均迁移百分比为66%，对于在位置4具有苯丙氨酸的两种肽为51%，并且对于在位置2具有苯丙氨酸的两种肽为41%。由于具有可检测的甲酰肽受体的人单核细胞的百分比的公开值为60%，因此显然在3位具有苯丙氨酸的两种四肽（fMet-Ile-Phe-Leu和fMet-Leu-Phe-Ile）是完全趋化性激动剂，其能够诱导所有携带受体的细胞的迁移。这与三肽fMet-Leu-Phe形成对比，其仅诱导50%的具有受体的单核细胞迁移（功效为33%）。由于趋化功效的六个四肽涵盖了很宽的范围内，该系列可能是有用的调查信号，导致定向运动后，受体的化学引诱剂占领。
We recently isolated, from culture fluids of Staphylococcus aureus, a chemotactic peptide that comprised equimolar quantities of methionine, leucine, phenylalanine, and isoleucine. It interacted with the formylmethionyl peptide receptor of human leukocytes and had considerably higher potency and efficacy than the widely studied tripeptide agonist fMet-Leu-Phe. On the assumption that the attractant was a formylmethionyl tetrapeptide, we synthesized the six possible sequences and tested the products for chemotactic potency and efficacy, as well as their capacity to inhibit binding of fluorescein isothiocyanate-labeled fMet-Leu-Phe-Lys to human monocytes. The concentrations required for inhibition of fluorescein-labeled fMet-Leu-Phe-Lys binding by the six peptides covered three orders of magnitude. Chemotactic potency (concentration that caused 50% of the maximum chemotactic response) ranged from 3.1 X 10(-11) M to 6.4 X 10(-10) M; efficacy (percentage of monocytes migrating at optimal attractant concentration) ranged from 41% to 66%. When the six synthetic tetrapeptides were ranked for chemotactic efficacy, they paired according to the position of phenylalanine. The average percentage migration was 66% for the two peptides with phenylalanine in position 3, 51% for phenylalanine in position 4, and 41% for phenylalanine in position 2. Since the published value for the percentage of human monocytes with detectable formyl peptide receptors is 60%, it is apparent that the two tetrapeptides with phenylalanine in position 3 (fMet-Ile-Phe-Leu and fMet-Leu-Phe-Ile) are full chemotactic agonists, which are capable of inducing migration of all the receptor-bearing cells. This is in contrast to the tripeptide fMet-Leu-Phe, which induces migration of only 50% of monocytes with receptors (efficacy of 33%). Since the chemotactic efficacy of the six tetrapeptides covers a wide range, the series may be useful to investigate signals that lead to directed movement after occupancy of receptors by chemoattractants.