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7634309 
Journal Article 
Design, synthesis and ribosome binding of chloramphenicol nucleotide and intercalator conjugates 
Johansson, D; Jessen, CH; Pøhlsgaard, J; Jensen, KB; Vester, B; Pedersen, EB; Nielsen, P; , 
2005 
Yes 
Bioorganic & Medicinal Chemistry Letters
ISSN: 0960-894X
EISSN: 1464-3405 
PERGAMON-ELSEVIER SCIENCE LTD 
OXFORD 
15 
8 
2079-2083 
English 
15808472 
WOS:000228432900024 
Molecular modelling based on X-ray structures of the antibiotic drug chloramphenicol bound in a bacterial ribosome has been used for design of chloramphenicol derivatives. Conjugates of the chloramphenicol amine through appropriate linkers to either a pyrene moiety or to a mono- or dinucleotide moiety were designed to improve binding to ribosomes by providing specific interactions in the peptidyl transferase site or to the P-loop in the ribosome. Specific binding of the conjugates were investigated by footprinting analysis using chemical modifications of accessible nucleotides in ribosomal RNA. The pyrene chloramphenicol conjugate shows enhanced binding to the chloramphenicol binding site compared to the native chloramphenicol, whereas the four nucleotide conjugates could not be shown to bind to the chloramphenicol binding site or to the P-loop. 
Antibiotics; Conjugates; Footprinting; Nucleic acids