Novel antibiotics: macrocyclic peptides designed to trap Holliday junctions.
[reaction: see text] Described are the syntheses of eight macrocyclic peptides designed to trap Holliday junctions in bacteria, thereby inhibiting bacterial growth. These macrocycles were designed from linear dimerized hexapeptides that bind to the C-2 symmetrical Holliday junction. They were synthesized from three monomers using a combinatorial-like strategy that permits elucidation of the monomer role in accumulation of Holliday junctions and antibiotic activity. These macrocycles are an important step in designing and synthesizing a new class of antibiotics.
Bolla
Megan L
ML
Department of Chemistry, Molecular Biology Institute, and Center for Applied and Experimental Genomics, 5500 Campanile Drive, 208 CSL, San Diego State University, San Diego, California 92182-1030, USA.
Azevedo
Enrique V
EV
Smith
Jason M
JM
Taylor
Rachel E
RE
Ranjit
Dev K
DK
Segall
Anca M
AM
McAlpine
Shelli R
SR
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D004269:DNA, Bacterial / Q000037:antagonists & inhibitors*; D004274:DNA, Recombinant; D015195:Drug Design; D010456:Peptides, Cyclic / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D004274:DNA, Recombinant; D010456:Peptides, Cyclic