DNA binding ligands with in vivo efficacy in murine models of bacterial infection: optimization of internal aromatic amino acids.
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).
Bürli
Roland W
RW
Genesoft Pharmaceuticals, 7300 Shoreline Court, South San Francisco, CA 94080, USA.
Kaizerman
Jacob A
JA
Duan
Jian-Xin
JX
Jones
Peter
P
Johnson
Kirk W
KW
Iwamoto
Mari
M
Truong
Kiet
K
Hu
Wenhao
W
Stanton
Timothy
T
Chen
Alfred
A
Touami
Sofia
S
Gross
Matthew
M
Jiang
Vernon
V
Ge
Yigong
Y
Moser
Heinz E
HE
D024322:Amino Acids, Aromatic / Q000737:chemistry*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D004195:Disease Models, Animal; D008024:Ligands; D008171:Lung Diseases / Q000188:drug therapy / Q000382:microbiology; D051379:Mice; D010538:Peritonitis / Q000188:drug therapy / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000302:isolation & purification; D013290:Streptococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000302:isolation & purification
D024322:Amino Acids, Aromatic; D000900:Anti-Bacterial Agents; D008024:Ligands; D004247:DNA