title: Molecular Design, Structural Analysis and Antifungal Activity of Derivatives of Peptide CGA-N46.
abstract: Chromogranin A (CGA)-N46, a derived peptide of human chromogranin A, has antifungal activity. To further research the active domain of CGA-N46, a series of derivatives were designed by successively deleting amino acid from both terminus of CGA-N46, and the amino acid sequence of each derivative was analyzed by bioinformatic software. Based on the predicted physicochemical properties of the peptides, including half-life time in mammalian reticulocytes (in vitro), yeast (in vivo) and E. coli (in vivo), instability index, aliphatic index and grand average of hydropathicity (GRAVY), the secondary structure, net charge, the distribution of hydrophobic residues and hydrophilic residues, the final derivatives CGA-N15, CGA-N16, CGA-N12 and CGA-N8 were synthesized by solid-phase peptide synthesis. The results of bioinformatic analysis showed that CGA-N46 and its derivatives were α-helix, neutral or weak positive charge, hydrophilic, and CGA-N12 and CGA-N8 were more stable than the other derivatives. The results of circular dichroism confirmed that CGA-N46 and its derived peptides displayed α-helical structure in an aqueous solution and 30 mM sodium dodecylsulfate, but α-helical contents decreased in hydrophobic lipid vesicles. CGA-N15, CGA-N16, CGA-N12 and CGA-N8 had higher antifungal activities than their mother peptide CGA-N46. Among of the derived peptides, CGA-N12 showed the least hemolytic activity. In conclusion, we have successfully identified the active domain of CGA-N46 with strong antifungal activity and weak hemolytic activity, which provides the possibility to develop a new class of antibiotics.
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, 450001, China. 1375098398@qq.com.
authors.forename: Rui-Fang
authors.initials: RF
authors.lastname: Li
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, 450001, China.
authors.forename: Zhi-Fang
authors.initials: ZF
authors.lastname: Lu
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, 450001, China.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Sun
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, 450001, China.
authors.forename: Shi-Hua
authors.initials: SH
authors.lastname: Chen
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, 450001, China.
authors.forename: Yan-Jie
authors.initials: YJ
authors.lastname: Yi
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, 450001, China.
authors.forename: Hui-Ru
authors.initials: HR
authors.lastname: Zhang
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, 450001, China.
authors.forename: Shuo-Ye
authors.initials: SY
authors.lastname: Yang
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, 450001, China.
authors.forename: Guang-Hai
authors.initials: GH
authors.lastname: Yu
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, 450001, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Huang
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, 450001, China.
authors.forename: Chao-Nan
authors.initials: CN
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology*; D053379:Chromogranin A / Q000737:chemistry; D002942:Circular Dichroism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D010455:Peptides / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D053379:Chromogranin A; D010455:Peptides
keywords: Antifungal activity; Antifungal peptides; Bioinformatic analysis; CGA-N46; Derived peptide; Hemolytic activity; Molecular design; Structural analysis