title: Diastereomeric selective effects for growth inhibition of synthesized mini parallel double-stranded peptides on Escherichia coli and Staphylococcus aureus.
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.
authors.affiliation: Department of Analytical Chemistry of Medicines, Showa Phamaceutical University, Tokyo, Japan. kobayasi@ac.shoyaku.ac.jp
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Nahomi
authors.initials: N
authors.lastname: Atuchi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Akiko
authors.initials: A
authors.lastname: Shiraishi
authors.forename: Hajime
authors.initials: H
authors.lastname: Hamashima
authors.forename: Akira
authors.initials: A
authors.lastname: Tanaka
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects; D002942:Circular Dichroism; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides