Mucha Piotr, Ruczyński Jarosław, Prochera Katarzyna, Rekowski Piotr
Laboratory of Biologically Active Compounds Chemistry, Department of Molecular Biochemistry, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland.
Int J Mol Sci. 2025 Aug 23;26(17):8184. doi: 10.3390/ijms26178184.
The emergence of multi-drug-resistant bacteria (known as superbugs) represents one of the greatest challenges for human health and modern medicine. Due to their remarkable ability to rapidly develop resistance to currently used antibiotics, new molecular targets for bacteria and substances capable of effectively combating related infections are still being sought. Lasso (known also as lariat) peptides are an unusual subclass of ribosomally synthesized and post-translationally modified peptides (RiPPs) with a structurally constrained knotted fold resembling a lasso. They are synthesized by certain groups of microorganisms as a result of complex processes involving intricate structural changes leading to the formation of the lasso structure. Reproducing these processes using known peptide synthesis methods poses a major challenge for synthetic chemistry. Lasso peptides exhibit a range of bioactivities including antibacterial activity. Due to the lasso structure, the peptides are capable of binding to new molecular targets, including atypical sides of ribosomes, in relation to currently used antibiotics. Thus, creating new mechanisms that inhibit metabolic processes leading to the death of pathogenic bacteria. This feature makes lasso peptides a potential "last chance" weapon in the fight against emerging superbugs.
多重耐药细菌（即所谓的超级细菌）的出现是人类健康和现代医学面临的最大挑战之一。由于它们对目前使用的抗生素迅速产生耐药性的非凡能力，仍在寻找针对细菌的新分子靶点以及能够有效对抗相关感染的物质。套索肽（也称为套索）是核糖体合成和翻译后修饰肽（RiPPs）的一个特殊亚类，具有类似于套索的结构受限的打结折叠。它们是由某些微生物群体通过复杂的过程合成的，这些过程涉及导致套索结构形成的复杂结构变化。使用已知的肽合成方法重现这些过程对合成化学构成了重大挑战。套索肽表现出一系列生物活性，包括抗菌活性。由于套索结构，这些肽能够结合新的分子靶点，包括与目前使用的抗生素相关的核糖体非典型面。因此，创造了抑制导致病原菌死亡的代谢过程的新机制。这一特性使套索肽成为对抗新兴超级细菌的潜在“最后机会”武器。
