Mechanism of interaction of the antileukemic drug cytosine arabinoside with aromatic peptides: role of sugar conformation and peptide backbone.
Interaction of the antileukemic drugs, cytosine-arabinoside (Ara-C) and adenosine-arabinoside (Ara-A) and a structural analogue, cytidine, with aromatic dipeptides has been studied by fluorescence and NMR spectroscopy. Ara-C and cytidine bind tryptophanyl and histidyl dipeptides but not tyrosyl dipeptides, while Ara-A does not bind to any of them. Both studies indicate association involving stacking of aromatic moieties. NMR spectra also indicate a protonation of the histidine moiety by Ara-C. In case of cytidine, the chemical shifts observed on binding to His-Phe imply that the backbone protons of the dipeptide participate in the binding. The conformation of the sugar and the base seem to play a very important role in the binding phenomenon as three similar molecules, Ara-C, Ara-A and cytidine bind in totally different ways.
Datta
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G
Biochemistry Division, Bhabha Atomic Research Centre, Trombay, Bombay, India.
Hosur
R V
RV
Verma
N C
NC
Khetrapal
C L
CL
Gurnani
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S
D000595:Amino Acid Sequence; D002236:Carbohydrate Conformation; D002241:Carbohydrates / Q000737:chemistry*; D003561:Cytarabine / Q000737:chemistry*; D003562:Cytidine / Q000737:chemistry; D003596:Cytosine / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D013050:Spectrometry, Fluorescence
D002241:Carbohydrates; D010455:Peptides; D003561:Cytarabine; D003562:Cytidine; D003596:Cytosine