1365564-13-1Relevant articles and documents
Synthesis of anticancer heptapeptides containing a unique lipophilic β2,2-amino acid building block
Torfoss, Veronika,Ausbacher, Dominik,Cavalcanti-Jacobsen, Cristiane de A.,Hansen, Terkel,Brandsdal, Bjorn-Olav,Havelkova, Martina,Strom, Morten B.
scheme or table, p. 170 - 176 (2012/06/29)
We report a series of synthetic anticancer heptapeptides (H-KKWβ2,2WKK-NH2) containing eight different central lipophilic β2,2-amino acid building blocks, which have demonstrated high efficiency when used as scaffolds in small cationic antimicrobial peptides and peptidomimetics. The most potent peptides in the present study had IC50 values of 9-23μm against human Burkitt's lymphoma and murine B-cell lymphoma and were all nonhaemolytic (EC50>200μm). The most promising peptide 10e also demonstrated low toxicity against human embryonic lung fibroblast cells and peripheral blood mononuclear cells and exceptional proteolytic stability.
Synthesis of cationic antimicrobial β2′2-amino acid derivatives with potential for oral administration
Hansen, Terkel,Ausbacher, Dominik,Flaten, Goril E.,Havelkova, Martina,Str?m, Morten B.
supporting information; experimental part, p. 858 - 868 (2011/04/18)
We have prepared a series of highly potent achiral cationic β 2, 2-amino acid derivatives that fulfill the Lipinski's rule of five and that contain the basic structural requirements of short cationic antimicrobial peptides. Highest antimicrobial potency was observed for one of the smallest β2, 2-amino acid derivatives (Mw 423.6exhibiting a MIC of 3.8 μM against methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), and Staphylococcus aureus, and 7.7 μM against Escherichia coli. The β 2, 2-amino acid derivatives were shown to have similar absorption properties as several commercially available drugs, and the results implied a resembling membrane disrupting mechanism of action as reported for much larger cationic antimicrobial peptides. By their high potency, nontoxicity, absorption properties, and ease of synthesis, the β2, 2-amino acid derivatives demonstrate a way to modify a vastly investigated class of cationic antimicrobial peptides into small druglike molecules with high commercial potential.
Antimicrobial activity of small β-peptidomimetics based on the pharmacophore model of short cationic antimicrobial peptides
Hansen, Terkel,Alst, Tore,Havelkova, Martina,Str?m, Morten B.
experimental part, p. 595 - 606 (2010/06/19)
We have synthesized a series of small β-peptidomimetics (Mw 2,2-amino acid coupled to a C-terminal L-arginine amide residue. By varying the lipophilic side-chains of the β2,2-amino acids, we obtained a series of highly potent β-peptidomimetics with high enzymatic stability against α-chymotrypsin and a general low toxicity against human erythrocytes. The most potent β-peptidomimetics displayed minimal inhibitory concentrations of 2.1-7.2 μM against Staphylococcus aureus, methicillin resistant Staphylococcus aureus (MRSA), methicillin resistant Staphylococcus epidermidis (MRSE), and Escherichia coli. Small amphipathic β-peptidomimetics may be a promising class of antimicrobial agents by means of having a similar range of potency and selectivity as larger cationic antimicrobial peptides in addition to improved enzymatic stability and lower costs of production.
