Antibacterial Activity of Peptides Related to Alafosfalin. The Effect of Varying the Aminophosphonate Fragment |
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Authors: | Barbara Lejczak Pawel Kafarski Helena Sztajer Przemyslaw Mastalerz |
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Affiliation: | Institute of Organic and Physical Chemistry, Technical University , Wroclaw , Poland |
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Abstract: | Abstract A series of 32 dipeptides containing N-terminal alanine or leu-cine and a variety of racemic 1-aminoalkanephosphonic acids vere prepared by standard procedures and tested for growth inhibition of six bacterial species (Escherichia coli, Klebsiella aerogenes, Serratia mercescens, Staphylococcus aureus, Streptococcus faeca-lis and Bacillus subtilis). The aminophosphonate residues were racemic and included Va1P, LeuP, ProP, PheP, α-methyl-AlaP, Glu-α-P, O-methyl-DOPAP, cyclohexane-1-amino-1-phosphonic acid, t-LeuP, O-acetyl-SerP, and GlyP derivatives RCH(NH2)PO3H2 where R=cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and adaman-tyl. N-Ala and N-Leu peptides of racemic AlaP were used as positive control. MIC and IC50 values indicate that the peptides containing 4-amino-4-phosphonobutyric acid (Glu-α-P) and α-methyl-AlaP are potent antibiotics, comparable in activity with LeuAlaP and AlaAlaP (Alafosfalin). Weak activity was observed for peptides of ProP, LeuP, ValP, PheP, cyclohexane-1-amino-1-phosphonic acid and 1-aminocyclopentylmethanephosphonic acid. While the activity of the α-methyl-AlaP peptides may be explained by inhibition of alanine racemase, the mechanism of action of the Glu-α-P peptides remains unknown. |
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