Kyotorphin (KTP, l-tyrosyl-l-arginine) is an endogenous analgesic neuropeptide first isolated from bovine brain in 1979. Previous studies have shown that kyotorphins possess anti-inflammatory and antimicrobial activity. Six kyotorphins-KTP-NH2, KTP-NH2-DL, ibuprofen-conjugated KTP (IbKTP), IbKTP-NH2, N-methyl-D-Tyr-L-Arg, and N-methyl-L-Tyr-D-Arg-were designed and synthesized to improve lipophilicity and resistance to enzymatic degradation. This study assessed the antimicrobial and antibiofilm activity of these peptides. The antifungal activity of kyotorphins was determined in representative strains of Candida species, including Candida albicans ATCC 10231, Candida krusei ATCC 6258, and six clinical isolates-Candida dubliniensis 19-S, Candida glabrata 217-S, Candida lusitaniae 14-S, Candida novergensis 51-S, Candida parapsilosis 63, and Candida tropicalis 140-S-obtained from the oral cavity of HIV-positive patients. The peptides were synthesized by standard solution or solid-phase synthesis, purified by RP-HPLC (purity >95 %), and characterized by nuclear magnetic resonance. The results of the broth microdilution assay and scanning electron microscopy showed that IbKTP-NH2 presented significant antifungal activity against Candida strains and antibiofilm activity against the clinical isolates. The absence of toxic activity and survival after infection was assessed after injecting the peptide in larvae of Galleria mellonella as experimental infection model. Furthermore, IbKTP-NH2 had strong antimicrobial activity against multidrug-resistant bacteria and fungi and was not toxic to G. mellonella larvae up to a concentration of 500 mM. These results suggest that IbKTP-NH2, in addition to its known effect on cell membranes, can elicit a cellular immune response and, therefore, is promising for biomedical application.

中文翻译：

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京都啡肽衍生物的抗真菌和抗生物膜活性

京都啡肽 (KTP, l-tyrosyl-l-arginine) 是一种内源性镇痛神经肽，于 1979 年首次从牛脑中分离出来。先前的研究表明，kyotorphins 具有抗炎和抗菌活性。六种kyotorphins-KTP-NH2、KTP-NH2-DL、布洛芬偶联的KTP (IbKTP)、IbKTP-NH2、N-甲基-D-Tyr-L-Arg和N-甲基-L-Tyr-D-Arg-被设计和合成以提高亲脂性和对酶促降解的抵抗力。本研究评估了这些肽的抗菌和抗生物膜活性。kyotorphins 的抗真菌活性在念珠菌属的代表性菌株中测定，包括白色念珠菌 ATCC 10231、克柔念珠菌 ATCC 6258 和六种临床分离株 - 都柏林念珠菌 19-S、光滑念珠菌 217-S、念珠菌 14 念珠菌、无念珠菌51-S，近平滑念珠菌 63，和热带假丝酵母 140-S-从 HIV 阳性患者的口腔中获得。肽段采用标准溶液或固相合成法合成，反相高效液相色谱法纯化（纯度>95%），核磁共振表征。肉汤微量稀释测定和扫描电子显微镜的结果表明，IbKTP-NH2 对念珠菌菌株具有显着的抗真菌活性，对临床分离株具有抗生物膜活性。在将肽注射到大蜡螟幼虫中作为实验感染模型后，评估了感染后没有毒性活性和存活率。此外，IbKTP-NH2 对多重耐药细菌和真菌具有很强的抗菌活性，并且在浓度高达 500 mM 时对 G. mellonella 幼虫无毒。这些结果表明 IbKTP-NH2、