Lactoferrin (LF) is a naturally occurring antimicrobial peptide that is cleaved by pepsin to lactoferricin (LFcin). LFcin has an enhanced antimicrobial activity as compared to that of LF. Recently several hetero- and homodimeric antimicrobial peptides stabilized by a single disulfide bond linking linear polypeptide chains have been discovered. We have demonstrated that the S–S bond heterodimerization of lipopeptide Laur-Orn-Orn-Cys–NH₂ (peptide III) and the synthetic N-terminal peptide of human lactoferricin (peptide I) yields a dimer (peptide V), which is almost as microbiologically active as the more active monomer and at the same time it is much less toxic. Furthermore, it has been found that the S–S bond homodimerization of both peptide I and peptide III did not affect antimicrobial and haemolytic activity of the compounds. The homo- and heterodimerization of peptides I and III resulted in either reduction or loss of antifungal activity. This work suggests that heterodimerization of antimicrobial lipopeptides via intermolecular disulfide bond might be a powerful modification deserving consideration in the design of antimicrobial peptides.

中文翻译：

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脂肽Laur-Orn-Orn-Cys-NH2和人乳铁蛋白的N端肽的二聚化对生物活性的影响。

乳铁蛋白（LF）是一种天然存在的抗菌肽，可被胃蛋白酶切割成乳铁蛋白（LFcin）。与LF相比，LFcin具有增强的抗菌活性。最近，已发现通过连接线性多肽链的单个二硫键稳定的几种异二聚体和同二聚体抗菌肽。我们已经证明脂肽Laur-Orn-Orn-Cys-NH ₂（肽III）和合成N的S–S键异二聚人乳铁蛋白的末端肽（肽I）产生二聚体（肽V），其在微生物学上的活性与活性更高的单体几乎一样，同时毒性也低得多。此外，已经发现肽I和肽III的S–S键均二聚化不会影响化合物的抗菌和溶血活性。肽I和III的均二聚和异二聚导致抗真菌活性降低或丧失。这项工作表明抗菌脂肽通过分子间二硫键的异二聚化可能是一个强大的修饰，值得在抗菌肽的设计中加以考虑。