The pharmacophore of short cationic antibacterial peptides.

Cationic antibacterial peptides have been proclaimed as new drugs against multiresistant bacteria. Their limited success so far is partially due to the size of the peptides, which gives rise to unresolved issues regarding administration, bioavailability, metabolic stability, and immunogenicity. We have systematically investigated the minimum antibacterial motif of cationic antibacterial peptides regarding charge and lipophilicity/bulk and found that the pharmacophore was surprisingly small, opening the opportunity for development of short antibacterial peptides for systemic use.

[1]  J. Svendsen,et al.  Antimicrobial activity of short arginine‐ and tryptophan‐rich peptides , 2002, Journal of peptide science : an official publication of the European Peptide Society.

[2]  J. Svendsen,et al.  Synthesis of a 2‐arylsulphonylated tryptophan: the antibacterial activity of bovine lactoferricin peptides containing Trp(2‐Pmc) , 2002, Journal of peptide science : an official publication of the European Peptide Society.

[3]  J. Svendsen,et al.  Simple parameterization of non‐proteinogenic amino acids for QSAR of antibacterial peptides , 2002, Journal of peptide science : an official publication of the European Peptide Society.

[4]  J. Toney Iseganan (IntraBiotics pharmaceuticals). , 2002, Current opinion in investigational drugs.

[5]  M. Zasloff Antimicrobial peptides of multicellular organisms , 2002, Nature.

[6]  J. Svendsen,et al.  The effects of charge and lipophilicity on the antibacterial activity of undecapeptides derived from bovine lactoferricin , 2002, Journal of peptide science : an official publication of the European Peptide Society.

[7]  J. Svendsen,et al.  Bulky aromatic amino acids increase the antibacterial activity of 15‐residue bovine lactoferricin derivatives , 2001, Journal of peptide science : an official publication of the European Peptide Society.

[8]  W. DeGrado,et al.  De Novo Design, Synthesis, and Characterization of Antimicrobial β-Peptides , 2001 .

[9]  J. Svendsen,et al.  The role of tryptophan in the antibacterial activity of a 15‐residue bovine lactoferricin peptide , 2001, Journal of peptide science : an official publication of the European Peptide Society.

[10]  J. Svendsen,et al.  Antibacterial activity of 15-residue lactoferricin derivatives. , 2000, The journal of peptide research : official journal of the American Peptide Society.

[11]  R. Hancock,et al.  The role of antimicrobial peptides in animal defenses. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[12]  T. Falla,et al.  IB-367, a Protegrin Peptide with In Vitro and In Vivo Activities against the Microflora Associated with Oral Mucositis , 2000, Antimicrobial Agents and Chemotherapy.

[13]  E. Krause,et al.  Peptide helicity and membrane surface charge modulate the balance of electrostatic and hydrophobic interactions with lipid bilayers and biological membranes. , 1996, Biochemistry.

[14]  M. Tomita,et al.  A review: The active peptide of lactoferrin , 1994, Acta paediatrica Japonica : Overseas edition.

[15]  R. Houghten,et al.  Generation and use of synthetic peptide combinatorial libraries for basic research and drug discovery , 1991, Nature.

[16]  D. Hultmark,et al.  Sequence and specificity of two antibacterial proteins involved in insect immunity , 1981, Nature.

[17]  H. G. Boman,et al.  Peptide antibiotics and their role in innate immunity. , 1995, Annual review of immunology.

[18]  R. Houghten,et al.  The antimicrobial activity of hexapeptides derived from synthetic combinatorial libraries. , 1995, The Journal of applied bacteriology.