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Synthesis of Well‐Defined Adenosine Diphosphate Ribose Oligomers
Authors:Hans A V Kistemaker  Lucien N Lameijer  Nico J Meeuwenoord  Prof Dr Herman S Overkleeft  Prof Dr Gijsbert A van der Marel  Dr Dmitri V Filippov
Institution:Leiden Institute of Chemistry, Department of Bio‐organic Synthesis, Leiden University, Einsteinweg 55, 2333 CC Leiden (The Netherlands) http://biosyn.lic.leidenuniv.nl/
Abstract:The post‐translational modification of proteins that is known as adenosine diphosphate ribosylation (ADPr) regulates a wide variety of important biological processes, such as DNA‐damage repair and cellular metabolism. This modification is also involved in carcinogenesis and the process of aging. Therefore, a better understanding of the function of ADP‐ribosylation is crucial for the development of novel therapeutics. To facilitate the elucidation of the biology of ADPr, the availability of well‐defined fragments of poly(ADP‐ribose) is essential. Herein we report a solid‐phase synthetic approach for the preparation of ADP‐ribose oligomers of exactly defined length. The methodology is exemplified by the first reported synthesis of an ADP‐ribose dimer and trimer.
Keywords:ADP‐ribosylation  phosphorylation  poly(ADP‐ribose)  pyrophosphates  solid‐phase synthesis
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