OpenLB
Open Library of Bioscience
Advanced Search
Chirality
Jan, 2024;36 (1): e23619.

Chiral recognition mechanism studies of Tyr-Arg-Phe-Lys-NH tetrapeptide on crown ether-based chiral stationary phase.

Toms Upmanis, Eduards Sevostjanovs, Helena Kažoka
Author Information
  1. Toms Upmanis: Latvian Institute of Organic Synthesis, Riga, Latvia. ORCID
  2. Eduards Sevostjanovs: Latvian Institute of Organic Synthesis, Riga, Latvia.
  3. Helena Kažoka: Latvian Institute of Organic Synthesis, Riga, Latvia.
PMID: 37700546 DOI: 10.1002/chir.23619

Abstract

Even though chiral recognition for crown-ether CSPs is generally understood, on a molecular level, exact mechanisms for the resolution are still unclear. Furthermore, short peptide analytes often contain multiple amino moieties capable of binding to the crown ether selector. In order to extend the understanding in chiral recognition mechanisms, polar organic mode separation of Tyr-Arg-Phe-Lys-NH tetrapeptide llll/dddd enantiomers on S- and R-(3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6 stationary phases was studied with 50-mM perchloric acid in methanol as mobile phase. Deviation from the generally acceptable 1:1 stoichiometry was supported by mass spectroscopy analysis of the formed complexes between tetrapeptide enantiomer and crown ether selectors, which revealed adducts possessing 1:1, 1:2, and 1:3 stoichiometry. Further investigation of complexation induced shifts by NMR indicated on different binding mechanisms between llll/dddd enantiomers of Tyr-Arg-Phe-Lys-NH and crown ether selectors. Enantioselective proton shifts were observed in studied tetrapeptide tyrosine and phenylalanine residues exclusively for llll enantiomer upon binding with S-(3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6 selector (and dddd enantiomer with R-(3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6 selector), indicating that these two amino acid residues contribute to chiral recognition. The obtained results were in agreement with the LC data.

Keywords

amino acids chiral recognition crown ether CSPs enantioselectivity tetrapeptide

References

  1. Teixeira J, Tiritan ME, Pinto MMM, Fernandes C. Chiral stationary phases for liquid chromatography: recent developments. Molecules. 2019;24(5):865. doi:10.3390/molecules24050865
  2. Chankvetadze B. Application of enantioselective separation techniques to bioanalysis of chiral drugs and their metabolites. TrAC Trends Anal Chem. 2021;143:116332. doi:10.1016/j.trac.2021.116332
  3. Tong S. Liquid-liquid chromatography in enantioseparations. J Chromatogr A. 2020;1626:461345. doi:10.1016/j.chroma.2020.461345
  4. Ianni F, Pucciarini L, Carotti A, Natalini S, Raskildina GZ, Sardella R. Last ten years (2008-2018) of chiral ligand-exchange chromatography in HPLC: an updated review. J Sep Sci. 2019;42(1):21-37. doi:10.1002/jssc.201800724
  5. Dumitrascuta M, Bermudez M, Ballet S, Wolber G, Spetea M. Mechanistic understanding of peptide analogues, DALDA, [Dmt1]DALDA, and KGOP01, binding to the Mu opioid receptor. Molecules. 2020;25(9):2087. doi:10.3390/molecules25092087
  6. Upmanis T, Kažoka H, Arsenyan P. A study of tetrapeptide enantiomeric separation on crown ether based chiral stationary phases. J Chromatogr A. 2020;1622:461152. doi:10.1016/j.chroma.2020.461152
  7. Upmanis T, Kažoka H. Mechanistic insights in chiral recognition of μ-opioid receptor agonist tetrapeptide on crown ether chiral stationary phase. J Chromatogr Open. 2021;1:100016. doi:10.1016/j.jcoa.2021.100016
  8. Upmanis T, Kažoka H. Influence of amino acid residue on chromatographic behaviour of μ-opioid receptor agonist tetrapeptide analogue on crown ether based chiral stationary phase. J Chromatogr A. 2022;1673:463059. doi:10.1016/j.chroma.2022.463059
  9. Carenzi G, Sacchi S, Abbondi M, Pollegioni L. Direct chromatographic methods for enantioresolution of amino acids: recent developments. Amino Acids. 2020;52(6-7):849-862. doi:10.1007/s00726-020-02873-w
  10. Upmanis T, Kažoka H. Application of commercially available crown ether chiral stationary phases for separation of tetrapeptide stereoisomers. Acta Pharm Hung. 2021;91(3-4):324-325. doi:10.33892/aph.2021.91(3-4).324-325
  11. Kyba EB, Kenji K, Sousa LR, Siegel MG, Cram DJ. Chiral recognition in molecular complexing. J Am Chem Soc. 1973;95(8):2692-2693. doi:10.1021/ja00789a051
  12. Avilés-Moreno JR, Quesada-Moreno MM, López-González JJ, Martínez-Haya B. Chiral recognition of amino acid enantiomers by a crown ether: chiroptical IR-VCD response and computational study. J Phys Chem B. 2013;117(32):9362-9370. doi:10.1021/jp405027s
  13. He J, Zheng Z-P, Zhu Q, Guo F, Chen J. Encapsulation mechanism of oxyresveratrol by β-cyclodextrin and hydroxypropyl-β-cyclodextrin and computational analysis. Molecules. 2017;22(11):1801. doi:10.3390/molecules22111801
  14. Ma S, Shen S, Lee H, et al. Vibrational circular dichroism of amylose carbamate: structure and solvent-induced conformational changes. Tetrahedron Asymmetry. 2008;19(18):2111-2114. doi:10.1016/j.tetasy.2008.08.027
  15. Bang E, Jung J-W, Lee W, Lee DW, Lee W. Chiral recognition of (18-crown-6)-tetracarboxylic acid as a chiral selector determined by NMR spectroscopy. J Chem Soc, Perkin Trans 2. 2001;9(9):1685-1692. doi:10.1039/b102026i
  16. Yashima E, Yamamoto C, Okamoto Y. NMR studies of chiral discrimination relevant to the liquid chromatographic enantioseparation by a cellulose phenylcarbamate derivative. J Am Chem Soc. 1996;118(17):4036-4048. doi:10.1021/ja960050x
  17. Czerwenka C, Zhang MM, Kählig H, Maier NM, Lipkowitz KB, Lindner W. Chiral recognition of peptide enantiomers by cinchona alkaloid derived chiral selectors: mechanistic investigations by liquid chromatography, NMR spectroscopy, and molecular modeling. J Org Chem. 2003;68(22):8315-8327. doi:10.1021/jo0346914
  18. Chankvetadze B. Combined approach using capillary electrophoresis and NMR spectroscopy for an understanding of enantioselective recognition mechanisms by cyclodextrins. Chem Soc Rev. 2004;33(6):337-347. doi:10.1039/b111412n
  19. Fejős I, Varga E, Benkovics G, et al. Comparative evaluation of the chiral recognition potential of single-isomer sulfated beta-cyclodextrin synthesis intermediates in non-aqueous capillary electrophoresis. J Chromatogr A. 2016;1467:454-462. doi:10.1016/j.chroma.2016.07.033
  20. Gerbaux P, De Winter J, Cornil D, et al. Noncovalent interactions between ([18]Crown-6)-tetracarboxylic acid and amino acids: electrospray-ionization mass spectrometry investigation of the chiral-recognition processes. Chem a Eur J. 2008;14(35):11039-11049. doi:10.1002/chem.200801372
  21. Schug KA, Maier NM, Lindner W. Deuterium isotope effects observed during competitive binding chiral recognition electrospray ionization-mass spectrometry of cinchona alkaloid-based systems. J Mass Spectrom. 2006;41(2):157-161. doi:10.1002/jms.983
  22. Czerwenka C, Lämmerhofer M, Maier NM, Rissanen K, Lindner W. Direct high-performance liquid chromatographic separation of peptide enantiomers: study on chiral recognition by systematic evaluation of the influence of structural features of the chiral selectors on enantioselectivity. Anal Chem. 2002;74(21):5658-5666. doi:10.1021/ac020372l
  23. Nagata H, Nishi H, Kamigauchi M, Ishida T. Structural scaffold of 18-crown-6 tetracarboxylic acid for optical resolution of chiral amino acid: X-ray crystal analyses and energy calculations of complexes of D- and L-isomers of tyrosine, isoleucine, methionine and phenylglycine. Org Biomol Chem. 2004;2(23):3470-3475. doi:10.1039/b409482d
  24. Peluso P, Chankvetadze B. Recognition in the domain of molecular chirality: from noncovalent interactions to separation of enantiomers. Chem Rev. 2022;122(16):13235-41300. doi:10.1021/acs.chemrev.1c00846
  25. De Gauquier P, Vanommeslaeghe K, Vander HY, Mangelings D. Modelling approaches for chiral chromatography on polysaccharide-based and macrocyclic antibiotic chiral selectors: a review. Anal Chim Acta. 2022;1198:338861. doi:10.1016/j.aca.2021.338861
  26. Lingenfelter DS, Helgeson RC, Cram DJ. Host-guest complexation. 23. High chiral recognition of amino acid and ester guests by hosts containing one chiral element. J Org Chem. 1981;46(2):393-406. doi:10.1021/jo00315a033
  27. Lämmerhofer M. Chiral recognition by enantioselective liquid chromatography: mechanisms and modern chiral stationary phases. J Chromatogr A. 2010;1217(6):814-856. doi:10.1016/j.chroma.2009.10.022
  28. Weinstein SE, Vining MS, Wenzel TJ. Lanthanide-crown ether mixtures as chiral NMR shift reagents for amino acid esters, amines and amino alcohols. Magn Reson Chem. 1997;35(4):273-280. doi:10.1002/(SICI)1097-458X(199704)35:4%3C273::AID-OMR73%3E3.0.CO;2-C

Grants

  1. IG-2022-08/Latvian Institute of Organic Synthesis
  2. IG-2021-05/Latvian Institute of Organic Synthesis

MeSH Term

Crown Ethers
Stereoisomerism
Tyrosine
Phenylalanine
Chromatography, High Pressure Liquid

Chemicals

(3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6
Crown Ethers
kyotorphin
Tyrosine
Phenylalanine
Journal Article

Word Cloud

Similar Articles

Cited By