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Main‐Chain Length Control of Conformation, Membrane Activity, and Antibiotic Properties of Lipopeptaibol Sequential Analogues
Author(s) -
Oancea Simona,
Hilma Geta,
Peggion Cristina,
Formaggio Fernando,
Toniolo Claudio
Publication year - 2008
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200890065
Subject(s) - chemistry , peptide , oligomer , membrane , circular dichroism , stereochemistry , micelle , amphiphile , amino acid , antibacterial activity , selectivity , peptide sequence , crystallography , combinatorial chemistry , aqueous solution , organic chemistry , biochemistry , bacteria , polymer , biology , gene , catalysis , genetics , copolymer
To investigate the effect of backbone length and amphiphilicity on the 3D structure, membrane permeability, and antibacterial properties of trichogins, a subclass of lipopeptaibols, we prepared, by the segment condensation approach in solution and chemically characterized, a set of N α ‐1‐octanoylated ‐X‐(GLUG) n ‐I‐L‐ ( X=G or U where U=Aib; n =1–4) sequential peptide esters. In parallel, the 12‐mer (UGGL) 3 aneurism peptide, an analogue of the 11‐mer sequential peptide ( n =2) with an amino acid insertion was also synthesized and studied. By FT‐IR absorption technique, we clearly showed that, in CDCl 3 solution, all peptides essentially populate intramolecularly H‐bonded, helical conformations. Moreover, CD spectroscopy indicates that all peptides, with the single exception of the shortest oligomer (the heptamer), adopt mixed 3 10 ‐/ α ‐helical structures, to an extent approximately correlating with main‐chain length, in MeOH solution and sodium dodecylsulfate (SDS) micelles. Significant membrane permeability properties were found only for the three longest GLUG‐based peptides, with the 15‐mer oligomer ( n =4) resulting the most active. The lack of activity exhibited by the aneurism peptide in this experiment strongly suggests a relevant role for the sequence amphiphilicity. In addition, antibacterial activity and selectivity were highlighted and demonstrated to be dependent on peptide main‐chain length and amphiphilicity, in the sense that the two shortest GLUG‐based homologues are active against Gram ‐positive strains, whereas the two longest homologues are able to penetrate the membranes of the Gram ‐negative strains, and the UGGL‐based aneurism peptide is inactive.