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Cyclotides from Brazilian Palicourea sessilis and Their Effects on Human Lymphocytes
Journal of Natural Products ( IF 3.3 ) Pub Date : 2021-01-04 , DOI: 10.1021/acs.jnatprod.0c01069 Meri Emili F Pinto 1, 2 , Lai Yue Chan 2 , Johannes Koehbach 2 , Seema Devi 3 , Carsten Gründemann 4 , Christian W Gruber 5 , Mario Gomes 6 , Vanderlan S Bolzani 1 , Eduardo Maffud Cilli 1 , David J Craik 2
Journal of Natural Products ( IF 3.3 ) Pub Date : 2021-01-04 , DOI: 10.1021/acs.jnatprod.0c01069 Meri Emili F Pinto 1, 2 , Lai Yue Chan 2 , Johannes Koehbach 2 , Seema Devi 3 , Carsten Gründemann 4 , Christian W Gruber 5 , Mario Gomes 6 , Vanderlan S Bolzani 1 , Eduardo Maffud Cilli 1 , David J Craik 2
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Cyclotides are plant-derived peptides found within five families of flowering plants (Violaceae, Rubiaceae, Fabaceae, Solanaceae, and Poaceae) that have a cyclic backbone and six conserved cysteine residues linked by disulfide bonds. Their presence within the Violaceae species seems ubiquitous, yet not all members of other families produce these macrocyclic peptides. The genus Palicourea Aubl. (Rubiaceae) contains hundreds of neotropical species of shrubs and small trees; however, only a few cyclotides have been discovered hitherto. Herein, five previously uncharacterized Möbius cyclotides within Palicourea sessilis and their pharmacological activities are described. Cyclotides were isolated from leaves and stems of this plant and identified as pase A–E, as well as the known peptide kalata S. Cyclotides were de novo sequenced by MALDI-TOF/TOF mass spectrometry, and their structures were solved by NMR spectroscopy. Because some cyclotides have been reported to modulate immune cells, pase A–D were assayed for cell proliferation of human primary activated T lymphocytes, and the results showed a dose-dependent antiproliferative function. The toxicity on other nonimmune cells was also assessed. This study reveals that pase cyclotides have potential for applications as immunosuppressants and in immune-related disorders.
中文翻译：
巴西 Palicourea sessilis 环肽及其对人淋巴细胞的影响
环肽是在五个开花植物科（堇菜科、茜草科、豆科、茄科和禾本科）中发现的植物源性肽，具有环状主链和六个通过二硫键连接的保守半胱氨酸残基。它们在堇菜科物种中的存在似乎无处不在，但并非其他科的所有成员都产生这些大环肽。 Palicourea Aubl 属。 （茜草科）包含数百种新热带灌木和小乔木；然而，迄今为止只发现了少数环肽。本文描述了Palicourea sessilis中五种先前未表征的莫比乌斯环肽及其药理活性。从该植物的叶和茎中分离出环肽，并鉴定为 pase A – E，以及已知的肽 kalata S。通过 MALDI-TOF/TOF 质谱法对环肽进行从头测序，并通过 NMR 光谱解析了其结构。由于一些环肽已被报道可调节免疫细胞，因此对 pase A – D 进行了人原代活化 T 淋巴细胞的细胞增殖检测，结果显示出剂量依赖性的抗增殖功能。还评估了对其他非免疫细胞的毒性。这项研究表明，pase 环肽具有作为免疫抑制剂和免疫相关疾病的应用潜力。
更新日期：2021-01-22
中文翻译：
巴西 Palicourea sessilis 环肽及其对人淋巴细胞的影响
环肽是在五个开花植物科（堇菜科、茜草科、豆科、茄科和禾本科）中发现的植物源性肽，具有环状主链和六个通过二硫键连接的保守半胱氨酸残基。它们在堇菜科物种中的存在似乎无处不在，但并非其他科的所有成员都产生这些大环肽。 Palicourea Aubl 属。 （茜草科）包含数百种新热带灌木和小乔木；然而，迄今为止只发现了少数环肽。本文描述了Palicourea sessilis中五种先前未表征的莫比乌斯环肽及其药理活性。从该植物的叶和茎中分离出环肽，并鉴定为 pase A – E，以及已知的肽 kalata S。通过 MALDI-TOF/TOF 质谱法对环肽进行从头测序，并通过 NMR 光谱解析了其结构。由于一些环肽已被报道可调节免疫细胞，因此对 pase A – D 进行了人原代活化 T 淋巴细胞的细胞增殖检测，结果显示出剂量依赖性的抗增殖功能。还评估了对其他非免疫细胞的毒性。这项研究表明，pase 环肽具有作为免疫抑制剂和免疫相关疾病的应用潜力。
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