A peptide fragment derived from the T-cell antigen receptor protein α-chain adopts β-sheet structure and shows potent antimicrobial activity

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2009-04, Vol.30 (4), p.647-653
• Main Authors: Zhang, Genghui, Lin, Xiaoyan, Long, Yi, Wang, Yanqiang, Zhang, Yueheng, Mi, Huaifeng, Yan, Husheng
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - metabolism; Anti-Bacterial Agents - pharmacology; Antibiotic; Antimicrobial peptide; Biological and medical sciences; Circular Dichroism; DNA - metabolism; Fundamental and applied biological sciences. Psychology; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Microbial Sensitivity Tests; Microscopy, Confocal; Microscopy, Electron, Scanning; Peptide; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Peptide Fragments - pharmacology; Protein Structure, Secondary; Receptors, Antigen, T-Cell, alpha-beta - chemistry; T-cell antigen receptor; Vertebrates: endocrinology; β-Sheet
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2008.12.002

A 9-residue peptide, CP-1 (GLRILLLKV-NH 2), is synthesized by solid-phase synthesis method. CP-1 is a C-terminal amidated derivative of a hydrophobic transmembrane segment (CP) of the T-cell antigen receptor (TCR) α-chain. CP-1 shows broad-spectrum antimicrobial activities against Gram-positive and Gram-negative bacteria with the minimal inhibitory concentration (MIC) values between 3 and 77 μM. Circular dichroism (CD) spectral data shows that CP-1 adopts a well-defined β-sheet structure in membrane-mimicking environments. CP-1 kills E. coli without lysing the cell membrane or forming transmembrane pores. However, CP-1 can penetrate the bacterial cell membranes and accumulate in the cytoplasm in both Gram-positive S. aureus and Gram-negative E. coli. Moreover CP-1 shows binding affinity for plasmid DNA. These results indicate that the killing mechanism of CP-1 likely involves the penetration into the cytoplasm and binding to intracellular components such as DNA.