DNA binding ligands with in vivo efficacy in murine models of bacterial infection: optimization of internal aromatic amino acids

Roland W Bürli; Jacob A Kaizerman; Jian-Xin Duan; Peter Jones; Kirk W Johnson; Mari Iwamoto; Kiet Truong; Wenhao Hu; Timothy Stanton; Alfred Chen; Sofia Touami; Matthew Gross; Vernon Jiang; Yigong Ge; Heinz E Moser

doi:10.1016/j.bmcl.2004.02.047

DNA binding ligands with in vivo efficacy in murine models of bacterial infection: optimization of internal aromatic amino acids

Bioorg Med Chem Lett. 2004 May 3;14(9):2067-72. doi: 10.1016/j.bmcl.2004.02.047.

Authors

Roland W Bürli¹, Jacob A Kaizerman, Jian-Xin Duan, Peter Jones, Kirk W Johnson, Mari Iwamoto, Kiet Truong, Wenhao Hu, Timothy Stanton, Alfred Chen, Sofia Touami, Matthew Gross, Vernon Jiang, Yigong Ge, Heinz E Moser

Affiliation

¹ Genesoft Pharmaceuticals, 7300 Shoreline Court, South San Francisco, CA 94080, USA.

PMID: 15080980
DOI: 10.1016/j.bmcl.2004.02.047

Abstract

DNA binding ligands with potent antimicrobial activity against Gram-positive bacteria were further optimized by variation of the internal aromatic amino acids. This modification led to compounds with improved in vivo efficacy in lethal murine models of peritonitis (methicillin-resistant S. aureus, MRSA) and lung infection (S. pneumoniae).

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Amino Acids, Aromatic / chemistry*
Animals
Anti-Bacterial Agents / metabolism
Anti-Bacterial Agents / pharmacology*
DNA / metabolism*
Disease Models, Animal
Ligands
Lung Diseases / drug therapy
Lung Diseases / microbiology
Mice
Peritonitis / drug therapy
Peritonitis / microbiology
Staphylococcal Infections / drug therapy*
Staphylococcal Infections / microbiology
Staphylococcus aureus / isolation & purification
Streptococcal Infections / drug therapy*
Streptococcal Infections / microbiology
Streptococcus pneumoniae / isolation & purification

Substances

Amino Acids, Aromatic
Anti-Bacterial Agents
Ligands
DNA