Incorporation of esters into proteins: Improved synthesis of hydroxyacyl tRNAs

We describe two synthetic advances in the preparation of acylated suppressor transfer RNAs which significantly enhance the ease with which alpha-hydroxy acids can be incorporated into protein structures using nonsense suppression methods. We demonstrate that, in most cases, protection of the alpha-hydroxy group in the acylation reaction is not necessary. In cases where protection of the alpha-hydroxy group is desired, we further demonstrate the efficacy of the TBDMS protecting group over the more standard o-nitrobenzyl-based protecting groups. These advances greatly simplify the protocol for incorporation of alpha-hydroxy acids into proteins, overcome limitations associated with photoreactive sidechains, and suggest a general approach to improved suppression yields. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.