Synthesis and solid-phase application of suitably protected γ-hydroxyvaline building blocks
Hydroxylated amino acids constitute an important modification in proteins. The best characterized of the post-translationally hydroxylated amino acids are γ-hydroxy-Pro (Hyp) and δ-hydroxy-Lys (Hyl), which are commonly found in collagen. Recently, an unexpected modified residue, γ-hydroxy-D-valine (D-Hyv), was identified within ribosomally expressed polypeptide chains of four conopeptides from the venoms of Conus gladiator and Conus mus.1These conopeptides were the first known examples of a naturally occurring polypeptide chain containing Hyv. In general, γ-hydroxyamino acids are not that common in nature (except γ-hydroxy-Pro) since a hydroxyl group in the γ-position can undergo intramolecular cyclization to form a lactone, cleaving the peptide bond. The stability of Hyv within conopeptides has been explained by the D-configuration at the α-carbon in conjunction with specific interactions with the surrounding L-amino acids. Given the wide range of neurophysiological...
KeywordsPolypeptide Chain Flash Chromatography Intramolecular Cyclization Potassium Ferrocyanide Lactone Formation
This work was supported by the Florida Sea Grant College Program (R/LR-MB-18), the National Institutes of Health (GM 066004 to F.M., CA 77402 to G.B.F.), and the FAU Center of Excellence in Biomedical and Marine Biotechnology.