Relevance of amphiphilicity and helicity on the antibacterial action of a histatin 5-derived peptide

IF 1.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Cristina Peggion, Valeria Panetta, Luana Lastella, Fernando Formaggio, Antonio Ricci, Simona Oancea, Geta Hilma, Barbara Biondi
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引用次数: 0

Abstract

Peptide dhvar4, derived from the active domain of our salivary peptide histatin 5, bears a Phe residue in the middle of its hydrophilic face when folded into an α-helix. We then synthesized an analog with this Phe replaced by Lys and two analogs preserving Phe but bearing two and three α-aminoisobutyric acid (Aib) residues to stabilize the helical structure. The aim of this design was to verify which of the two features is more favorable to the biological activity. We performed a conformational study by means of circular dichroism and nuclear magnetic resonance, made antibacterial tests, and assessed the stability of the peptides in human serum. We observed that amphiphilicity is more important than helix stability, provided a peptide can adopt a helical conformation in a membrane-mimetic environment.

Abstract Image

Abstract Image

两亲性和螺旋性对组蛋白 5 衍生肽抗菌作用的影响
多肽 dhvar4 来自唾液肽组蛋白 5 的活性结构域,在折叠成 α-helix 时,其亲水面的中间含有一个 Phe 残基。然后,我们合成了一个类似物,用 Lys 取代了 Phe,还合成了两个类似物,保留了 Phe,但含有两个和三个 α-氨基异丁酸(Aib)残基,以稳定螺旋结构。这一设计的目的是验证这两种特征中哪一种更有利于生物活性。我们通过圆二色性和核磁共振进行了构象研究,进行了抗菌测试,并评估了肽在人体血清中的稳定性。我们发现,只要多肽能在膜模拟环境中形成螺旋构象,两亲性就比螺旋稳定性更重要。
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来源期刊
Journal of Peptide Science
Journal of Peptide Science 生物-分析化学
CiteScore
3.40
自引率
4.80%
发文量
83
审稿时长
1.7 months
期刊介绍: The official Journal of the European Peptide Society EPS The Journal of Peptide Science is a cooperative venture of John Wiley & Sons, Ltd and the European Peptide Society, undertaken for the advancement of international peptide science by the publication of original research results and reviews. The Journal of Peptide Science publishes three types of articles: Research Articles, Rapid Communications and Reviews. The scope of the Journal embraces the whole range of peptide chemistry and biology: the isolation, characterisation, synthesis properties (chemical, physical, conformational, pharmacological, endocrine and immunological) and applications of natural peptides; studies of their analogues, including peptidomimetics; peptide antibiotics and other peptide-derived complex natural products; peptide and peptide-related drug design and development; peptide materials and nanomaterials science; combinatorial peptide research; the chemical synthesis of proteins; and methodological advances in all these areas. The spectrum of interests is well illustrated by the published proceedings of the regular international Symposia of the European, American, Japanese, Australian, Chinese and Indian Peptide Societies.
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