Determination of sequence and absolute configuration of peptide amino acids by HPLC–MS/CD-based detection of liberated N-terminus phenylthiohydantoin amino acids

June 28, 2022

Title

Determination of sequence and absolute configuration of peptide amino acids by HPLC–MS/CD-based detection of liberated N-terminus phenylthiohydantoin amino acids

Author

Dongyup Hahn, Weihong Wang, Hyukjae Choi & Heonjoong Kang

Year

2022

Journal

Scientific Reports

Abstract

We report a method for the simultaneous determination of the sequence and absolute configuration of peptide amino acids using a combination of Edman degradation and HPLC–MS/CD. Phenylthiohydantoin (PTH) derivatives of 20 pairs of standard d- and l-amino acids were synthesized by the Edman reaction. The CD spectra of the derivatives revealed that each pair of the PTH derivatives exhibited the absorption with opposite signs at around 270 nm. These standard PTH derivatives showed well-resolved resolution without interference from byproducts in the ion chromatogram and clear positive/negative CD absorptions when subjected on a reversed phase HPLC–MS system coupled with a CD-2095 HPLC detector. This method was applied for the detection of a synthetic pentapeptide and a natural depsipeptide (halicylindramide C). The sequence and configuration of the pentapeptide and up to eight residues of halicylindramide C were successfully analyzed by this method. The amino acid configuration of the pentapeptide was also determined successfully by subjecting its acid hydrolysates to the Edman reaction followed by HPLC–MS/CD.

Instrument

J-715, LC-2000

Keywords

peptide, amino acids, Edman reaction