Abstract
The synthesis of a series of mini double-stranded peptides containing chiral–x-Phe–y-Phe–peptide residues and the diastereomeric selective effects of these compounds on Escherichia coli NIHJ JC-2 and Staphylococcus aureus FDA 209P growth are described. In the case of bis(y-Phe–x-Phe)-N,N-ethane-1,2-diamine, bis(y-Phe–x-Phe)-N,N-buthane-1,4-diamine, bis(y-Phe–x-Phe)-N,N-hexane-1,6-diamine, and bis(y-Phe–x-Phe)-N,N-dodecane-1,12-diamine, etc., the four configurations, (L-, L-), (D-, L-), (L-, D-) and (D-, D-), where the symbols x- and y- represent optical isomers with L- and D- forms, were used to investigate the relationship between chirality and antibacterial activity. The level of activity increased in the following order: (L-, L-)<(D-, D-)<(L-, D-)<(D-, L-). The data show that (D-, L-) chilarity is more potent than (L-, L-) chilarity. Then, these results suggest that the –y-Phe–x-Phe Phe–sequence in the double-stranded peptide has anti-bacterial activity and the chirality of –y-Phe–x-Phe affects the anti-bacterial activity. Our results show that the uptake by penetration through the membrane of bis(y-Phe–x-Phe)2-Spacers is a first step in the expression of anti-bacterial activity. This study provides new insights in the chirality-antibacterial activity relationships of a series of mini double-stranded peptides.
