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.