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Volume 13, Issue 5, Pages (May 2006)

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1 Volume 13, Issue 5, Pages 531-538 (May 2006)
Mimicking Helical Antibacterial Peptides with Nonpeptidic Folding Oligomers  Aude Violette, Sylvie Fournel, Karen Lamour, Olivier Chaloin, Benoit Frisch, Jean-Paul Briand, Henri Monteil, Gilles Guichard  Chemistry & Biology  Volume 13, Issue 5, Pages (May 2006) DOI: /j.chembiol Copyright © 2006 Elsevier Ltd Terms and Conditions

2 Figure 1 Design of Amphipathic Cationic N,N′-Linked Oligoureas
(A) General formula of N,N′-linked oligoureas and schematic representation of the idealized (P)-2.512,14 helix (side view and top view) highlighting the five residue repeat. (B and C) Sequences and helical wheel representation of amphiphilic 2.5-helical oligoureas evaluated for antimicrobial activity. These oligoureas are exclusively composed of cationic side chains (β-HLysu, indicated by a plus sign) segregated on two-fifth (1–3, 5–13) or three-fifth (4) of the helix circumference and hydrophobic aliphatic (indicated by a closed circle) and aromatic (indicated by a closed circle) side chains. A terminal residue with a free amino group on the west side of the molecule is indicated by a plus sign and a closed circle or a plus sign and a closed circle in a box, while an N-capped terminus is indicated by a closed circle or a closed circle in a box. Chemistry & Biology  , DOI: ( /j.chembiol ) Copyright © 2006 Elsevier Ltd Terms and Conditions

3 Figure 2 Helix-Forming Propensity of Oligoureas Investigated by Circular Dichroism in Various Media at 0.5 mM · per Residue Molar Ellipticity in deg · cm2 · dmol−1 (A) Closed square, molecule 3 in MeOH; closed triangle, molecule 2 in MeOH. (B) Closed square molecule 12 in MeOH; closed triangle, molecule 13 in MeOH; open square, molecule 12 in HBS; open triangle molecule 13 in HBS (pH 7.4). (C) Closed square, molecule 10 in MeOH; closed triangle, molecule 6 in MeOH, open square, molecule 10 in HBS (pH 7.4); open triangle, molecule 6 in HBS (pH 7.4). (D) X, molecule 10 in HBS (pH 7.4); closed triangle, molecule 10 in zwitterionic liposomes (PC/Chol, 80:20, lipid/oligomer ratio of 5); closed square, molecule 10 in anionic liposomes (PC/PG 70:30, lipid/oligomer ratio of 10). (E) X, molecule 11 in HBS (pH 7.4); closed square, molecule 11 in anionic liposomes (PC/PG 70:30, lipid/oligomer ratio of 10). (F) X, molecule 3 in HBS (pH 7.4); closed square, molecule 3 in anionic liposomes (PC/PG 70:30, lipid/oligomer ratio of 10). Chemistry & Biology  , DOI: ( /j.chembiol ) Copyright © 2006 Elsevier Ltd Terms and Conditions

4 Figure 3 Hemolytic Activity and Stability of Oligoureas toward Proteolysis (A) Hemolytic activity measured at indicated concentrations of Melittin (closed triangle), molecule 10 (open square), molecule 14 (closed square), and molecule 15 (closed circle). (B) Proteolytic stability of molecule 13 evaluated by RP-HPLC after 5 days in mouse serum at 37°C. Chemistry & Biology  , DOI: ( /j.chembiol ) Copyright © 2006 Elsevier Ltd Terms and Conditions


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