Polymerase-catalyzed synthesis of DNA from phosphoramidate conjugates of deoxynucleotides and amino acids

• Published in: Nucleic acids research 2007-08, Vol.35 (15), p.5060-5072
• Main Authors: Adelfinskaya, O., Terrazas, M., Froeyen, M., Marlière, P., Nauwelaerts, K., Herdewijn, P.
• Format: Article
• Language: English
• Subjects: Adenosine Monophosphate - analogs & derivatives; Adenosine Monophosphate - chemistry; Adenosine Monophosphate - metabolism; Amides - chemical synthesis; Amides - chemistry; Amino Acids - chemistry; Aspartic Acid - analogs & derivatives; Aspartic Acid - chemistry; Aspartic Acid - metabolism; Catalysis; Deoxyadenine Nucleotides - chemistry; Deoxyadenine Nucleotides - metabolism; DNA - biosynthesis; DNA - chemistry; DNA Primers; DNA-Directed DNA Polymerase - metabolism; Histidine - analogs & derivatives; Histidine - chemistry; Histidine - metabolism; HIV - enzymology; Models, Molecular; Nucleic Acid Enzymes; Phosphoric Acids - chemical synthesis; Phosphoric Acids - chemistry; RNA-Directed DNA Polymerase - chemistry; RNA-Directed DNA Polymerase - metabolism; Stereoisomerism
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkm498

Some selected amino acids, in particular l-aspartic acid (l-Asp) and l-histidine (l-His), can function as leaving group during polymerase-catalyzed incorporation of deoxyadenosine monophosphate (dAMP) in DNA. Although l-Asp-dAMP and l-His-dAMP bind, most probably, in a different way in the active site of the enzyme, aspartic acid and histidine can be considered as mimics of the pyrophosphate moiety of deoxyadenosine triphosphate. l-Aspartic acid is more efficient than d-aspartic acid as leaving group. Such P-N conjugates of amino acids and deoxynucleotides provide a novel experimental ground for diversifying nucleic acid metabolism in the field of synthetic biology.