Latvian Institute of Organic Synthesis, 21 Aizkraukles Street, LV, 1006 Riga, Latvia.
Latvian Institute of Organic Synthesis, 21 Aizkraukles Street, LV, 1006 Riga, Latvia.
J Chromatogr A. 2022 Jun 21;1673:463059. doi: 10.1016/j.chroma.2022.463059. Epub 2022 Apr 20.
The influence of amino acid residue on μ-opioid receptor agonist tetrapeptide Tyr-Arg-Phe-Lys-NH analogue chromatographic behaviour on crown ether based chiral stationary phases has been investigated. S- and R-(3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6 chiral selectors in commercially available CROWNPAK CR-I (+) and (-) columns are both each other enantiomers, thus, under the same LC conditions, retention of Tyr-Arg-Phe-Lys-NHdxxx enantiomers (fixed in d-tyrosine position) on S-chiral selector do not significantly differ from the retention times of their lxxx antipodes, obtained on R-chiral selector (and vice versa), allowing us to study the apparent separation of a specific tetrapeptide enantiomeric pair, without obtaining the actual racemate. Ten tetrapeptides (llll-isomers) have been synthesized with the aim to cover a wider range of different amino acid classes. Histidine, glutamic acid, cysteine, leucine and tryptophan were introduced at the N-terminus or Phe position of Tyr-Arg-Phe-Lys-NH tetrapeptide structure. The effects of the amino acid residue with emphasis on retention, enantioseparation, as well as the influence of position of the amino acid residue in tetrapeptide sequence, are discussed.
研究了氨基酸残基对μ-阿片受体激动剂四肽 Tyr-Arg-Phe-Lys-NH 类似物在基于冠醚的手性固定相上色谱行为的影响。商业可得的 CROWNPAK CR-I(+)和(-)柱中的 S-和 R-（3,3'-二苯基-1,1'-联萘基）-20-冠-6 手性选择剂互为对映异构体，因此，在相同的 LC 条件下，Tyr-Arg-Phe-Lys-NHdxxx 对映体（固定在 d-酪氨酸位置）在 S-手性选择剂上的保留时间与在 R-手性选择剂上（反之亦然）获得的 lxxx 对映体的保留时间没有显著差异，使我们能够研究特定四肽对映体对的表观分离，而无需获得实际的外消旋体。合成了十个四肽（llll-异构体），旨在涵盖更广泛的不同氨基酸类别。在 Tyr-Arg-Phe-Lys-NH 四肽结构的 N 末端或 Phe 位置引入了组氨酸、谷氨酸、半胱氨酸、亮氨酸和色氨酸。讨论了氨基酸残基对保留、对映体分离的影响，以及氨基酸残基在四肽序列中的位置的影响。
