Incorporation of esters into proteins: Improved synthesis of hydroxyacyl tRNAs

We describe two synthetic advances in the preparation of acylated suppresso r transfer RNAs which significantly enhance the ease with which alpha-hydro xy acids can be incorporated into protein structures using nonsense suppres sion methods. We demonstrate that, in most cases, protection of the alpha-h ydroxy group in the acylation reaction is not necessary. In cases where pro tection of the alpha-hydroxy group is desired, we further demonstrate the e fficacy of the TBDMS protecting group over the more standard o-nitrobenzyl- based protecting groups. These advances greatly simplify the protocol for i ncorporation of alpha-hydroxy acids into proteins, overcome limitations ass ociated with photoreactive sidechains, and suggest a general approach to im proved suppression yields. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.