The quest for more specific drugs in antitumor chemotherapy led us to the design of anthraquinone-peptide conjugates capable of selective recognition of the nucleic acid. We present here the DNA binding characteristics, sequence specificity and geometry of interaction of a pair of enantiomers containing the lysine-glycine dipeptide in the side chains. The D enantiomer binds right handed double stranded DNA more efficiently than the L form under all conditions tested. The source of higher binding affinity is not electrostatic in nature and rests in the more favorable hydrophobic contacts of the D-lysyl side chains in the drug-DNA complex. Both derivatives exhibit preference for alternating GC base sequences and intercalate into DNA in a threading mode as suggested by chiroptical and theoretical studies. The D enantiomer, being a peptidyl derivative that contains a non-natural amino acid, has the considerable advantage of being less susceptible to enzymatic hydrolysis and could therefore represent a lead compound for further development.

Preferred interaction of D-peptidyl-anthraquinones with double-stranded B-DNA

GATTO, BARBARA;ZAGOTTO, GIUSEPPE;SISSI, CLAUDIA;PALUMBO, MANLIO
1997

Abstract

The quest for more specific drugs in antitumor chemotherapy led us to the design of anthraquinone-peptide conjugates capable of selective recognition of the nucleic acid. We present here the DNA binding characteristics, sequence specificity and geometry of interaction of a pair of enantiomers containing the lysine-glycine dipeptide in the side chains. The D enantiomer binds right handed double stranded DNA more efficiently than the L form under all conditions tested. The source of higher binding affinity is not electrostatic in nature and rests in the more favorable hydrophobic contacts of the D-lysyl side chains in the drug-DNA complex. Both derivatives exhibit preference for alternating GC base sequences and intercalate into DNA in a threading mode as suggested by chiroptical and theoretical studies. The D enantiomer, being a peptidyl derivative that contains a non-natural amino acid, has the considerable advantage of being less susceptible to enzymatic hydrolysis and could therefore represent a lead compound for further development.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/2462195
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