A peptide fragment derived from the T-cell antigen receptor protein alpha-chain adopts beta-sheet structure and shows potent antimicrobial activity.
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) alpha-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 77microM. Circular dichroism (CD) spectral data shows that CP-1 adopts a well-defined beta-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.
Zhang
Genghui
G
Ministry of Education, and Institute of Polymer Chemistry, Nankai University, Tianjin, PR China.
Lin
Xiaoyan
X
Long
Yi
Y
Wang
Yanqiang
Y
Zhang
Yueheng
Y
Mi
Huaifeng
H
Yan
Husheng
H
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004247:DNA