NAICONS Srl , Via Fantoli 16/15, 20138 Milano, Italy.
ACS Chem Biol. 2014 Feb 21;9(2):398-404. doi: 10.1021/cb400692w. Epub 2013 Nov 20.
Among the growing family of ribosomally synthesized, post-translationally modified peptides, particularly intriguing are class III lanthipeptides containing the triamino acid labionin. In the course of a screening program aimed at finding bacterial cell wall inhibitors, we discovered a new lanthipeptide produced by an Actinoplanes sp. The molecule, designated NAI-112, consists of 22 amino acids and contains an N-terminal labionin and a C-terminal methyl-labionin. Unique among lanthipeptides, it carries a 6-deoxyhexose moiety N-linked to a tryptophan residue. Consistently, the corresponding gene cluster encodes, in addition to the LanKC enzyme characteristic of this lanthipeptide class, a glycosyl transferase. Despite possessing weak antibacterial activity, NAI-112 is effective in experimental models of nociceptive pain, reducing pain symptoms in mice in both the formalin and the chronic constriction injury tests. Thus, NAI-112 represents, after the labyrinthopeptins, the second example of a lanthipeptide effective against nociceptive pain.
在不断增加的核糖体合成的翻译后修饰肽家族中，含有三氨基酸 labionin 的 III 类聚酮肽特别引人注目。在一个旨在寻找细菌细胞壁抑制剂的筛选计划中，我们发现了一种由 Actinoplanes sp 产生的新型聚酮肽。该分子被命名为 NAI-112，由 22 个氨基酸组成，含有一个 N 端 labionin 和一个 C 端甲基-labionin。与其他聚酮肽不同的是，它携带一个 N 连接到色氨酸残基的 6-去氧己糖部分。一致的是，相应的基因簇除了编码这种聚酮肽类的 LanKC 酶外，还编码一个糖基转移酶。尽管 NAI-112 具有较弱的抗菌活性，但它在伤害性疼痛的实验模型中有效，在福尔马林和慢性缩窄性损伤试验中均能减轻小鼠的疼痛症状。因此，NAI-112 是继 labyrinthopeptins 之后第二个对伤害性疼痛有效的聚酮肽。
