{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T04:27:58Z","timestamp":1773030478772,"version":"3.50.1"},"reference-count":57,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018818","name":"National Research, Development, and Innovation Office-NKFIA","doi-asserted-by":"publisher","award":["K137607"],"award-info":[{"award-number":["K137607"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018818","name":"National Research, Development, and Innovation Office-NKFIA","doi-asserted-by":"publisher","award":["\u00daNKP-23-3-SZTE-191"],"award-info":[{"award-number":["\u00daNKP-23-3-SZTE-191"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018818","name":"National Research, Development, and Innovation Office-NKFIA","doi-asserted-by":"publisher","award":["TKP2021-EGA-32"],"award-info":[{"award-number":["TKP2021-EGA-32"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]},{"name":"New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development, and Innovation Fund","award":["K137607"],"award-info":[{"award-number":["K137607"]}]},{"name":"New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development, and Innovation Fund","award":["\u00daNKP-23-3-SZTE-191"],"award-info":[{"award-number":["\u00daNKP-23-3-SZTE-191"]}]},{"name":"New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development, and Innovation Fund","award":["TKP2021-EGA-32"],"award-info":[{"award-number":["TKP2021-EGA-32"]}]},{"name":"Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund","award":["K137607"],"award-info":[{"award-number":["K137607"]}]},{"name":"Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund","award":["\u00daNKP-23-3-SZTE-191"],"award-info":[{"award-number":["\u00daNKP-23-3-SZTE-191"]}]},{"name":"Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund","award":["TKP2021-EGA-32"],"award-info":[{"award-number":["TKP2021-EGA-32"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Novel peptides based on common amino acid building blocks may serve as possible drug candidates; however, their flexible structures may require stabilization via the incorporation of conformational constraints. The insertion of unusual amino acids is a feasible option that may provide improved pharmacokinetic and pharmacodynamic properties of such peptide-type drugs. The stereochemical purity of these kinds of building blocks must be verified by an efficient separation technique, such as high-performance liquid chromatography. Here, we present and discuss the results of the stereoselective separation mechanism of \u00df-methylated phenylalanine (\u00df-MePhe), tyrosine (\u00df-MeTyr), 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (\u00df-MeTic), and cyclohexylalanine (\u00df-MeCha) together with non-methylated Phe, Tyr, Tic, and Cha applying Cinchona alkaloid-based chiral stationary phases (CSPs). The studied zwitterionic CSPs acting as ion exchangers provided optimal performance in the polar ionic mode when methanol or a mixture of methanol and acetonitrile was utilized as the mobile phase together with organic acid and base additives. It was found that the basicity of small amines applied as mobile phase additives did not directly influence the chromatographic ion exchange concept. However, the size of the amines and their concentration led to a reduced retention time following the principles of ion exchange chromatography. On the basis of a systematic study of the effects of the eluent composition on the chromatographic behavior, important structure\u2013retention and enantioselectivity relationships could be revealed. Through a temperature study, it has become evident that the composition of the eluent and the structure of analytes markedly affect the thermodynamic properties.<\/jats:p>","DOI":"10.3390\/ijms26094004","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T12:04:33Z","timestamp":1745409873000},"page":"4004","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["High-Performance Liquid Chromatographic Separation of Stereoisomers of \u00df-Methyl-Substituted Unusual Amino Acids Utilizing Ion Exchangers Based on Cinchona Alkaloids"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7312-8353","authenticated-orcid":false,"given":"G\u00e1bor","family":"N\u00e9meti","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Analysis, University of Szeged, Somogyi u. 4, H-6720 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9076-2177","authenticated-orcid":false,"given":"R\u00f3bert","family":"Berkecz","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Analysis, University of Szeged, Somogyi u. 4, H-6720 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D\u00e1niel","family":"Ozsv\u00e1r","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Analysis, University of Szeged, Somogyi u. 4, H-6720 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2432-8409","authenticated-orcid":false,"given":"Zsolt","family":"Szakonyi","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, University of Szeged, E\u00f6tv\u00f6s u. 6, H-6720 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Lindner","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, University of Vienna, W\u00e4hringer Strasse 38, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7446-2396","authenticated-orcid":false,"given":"Aleksandra","family":"Misicka","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Warsaw, Pasteura Str. 1, 02-093 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8909-4087","authenticated-orcid":false,"given":"Dagmara","family":"Tymecka","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Warsaw, Pasteura Str. 1, 02-093 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00e9za","family":"T\u00f3th","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Biological Research Centre, Temesv\u00e1ri krt. 62, H-6725 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antal","family":"P\u00e9ter","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Analysis, University of Szeged, Somogyi u. 4, H-6720 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8282-457X","authenticated-orcid":false,"given":"Istv\u00e1n","family":"Ilisz","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Analysis, University of Szeged, Somogyi u. 4, H-6720 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nrd.2017.232","article-title":"Automating drug discovery","volume":"17","author":"Schneider","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/s41573-019-0050-3","article-title":"Rethinking drug design in the artificial intelligence era","volume":"19","author":"Schneider","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.drudis.2014.10.003","article-title":"Peptide therapeutics: Current status and future directions","volume":"20","author":"Fosgerau","year":"2015","journal-title":"Drug Discov. Today"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1021\/cb300515u","article-title":"Getting in shape: Controlling peptide bioactivity and bioavailability using conformational constraints","volume":"8","author":"Bock","year":"2013","journal-title":"ACS Chem. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Bozovi\u010dar, K., and Bratkovi\u010d, T. (2021). Small and simple, yet sturdy: Conformationally constrained peptides with remarkable properties. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041611"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/S1367-5931(00)00148-4","article-title":"Unnatural amino acids as probes of protein structure and function","volume":"4","author":"Dougherty","year":"2000","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_7","first-page":"302","article-title":"\u00df-Amino acids: Role in human biology and medicinal chemistry\u2014A review","volume":"7","author":"Riaz","year":"2017","journal-title":"Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e202203906","DOI":"10.1002\/slct.202203906","article-title":"Construction of unusual amino acid derivatives and bis-fused oxacycles via ring-closing metathesis","volume":"7","author":"Kotha","year":"2022","journal-title":"ChemistrySelect"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1080\/1040841X.2022.2047008","article-title":"Unnatural amino acids: Promising implications for the development of new antimicrobial peptides","volume":"49","author":"Wang","year":"2023","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1042\/bj2680249","article-title":"Emerging approaches in the molecular design of receptor-selective peptide ligands: Conformational, topographical and dynamic considerations","volume":"268","author":"Hruby","year":"1990","journal-title":"Biochem. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"115648","DOI":"10.1016\/j.trac.2019.115648","article-title":"Recent trends in chiral supercritical fluid chromatography","volume":"120","author":"West","year":"2019","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11955","DOI":"10.1039\/D3SC01630G","article-title":"Strategies for chiral separation: From racemate to enantiomer","volume":"14","author":"Sui","year":"2023","journal-title":"Chem. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"115709","DOI":"10.1016\/j.trac.2019.115709","article-title":"Recent trends in preparation, investigation and application of polysaccharide-based chiral stationary phases for separation of enantiomers in high-performance liquid chromatography","volume":"122","author":"Chankvetadze","year":"2020","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1007\/s00726-020-02873-w","article-title":"Direct chromatographic methods for enantioresolution of amino acids: Recent developments","volume":"52","author":"Carenzi","year":"2020","journal-title":"Amino Acids"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"117733","DOI":"10.1016\/j.trac.2024.117733","article-title":"Enantioselective separation techniques in forensic analysis and clinical toxicology","volume":"175","author":"Tini","year":"2024","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"115634","DOI":"10.1016\/j.trac.2019.115634","article-title":"Advances in chiral multidimensional liquid chromatography","volume":"120","author":"Ali","year":"2019","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Teixeira, J., Tiritan, M.E., Pinto, M.M.M., and Fernandes, C. (2019). Chiral stationary phases for liquid chromatography: Recent developments. Molecules, 24.","DOI":"10.3390\/molecules24050865"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"115628","DOI":"10.1016\/j.trac.2019.115628","article-title":"Chiral recognition in separation sciences. Part II: Macrocyclic glycopeptide, donor-acceptor, ion-exchange, ligand-exchange and micellar selectors","volume":"119","author":"Scriba","year":"2019","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"115639","DOI":"10.1016\/j.trac.2019.115639","article-title":"Chiral recognition in separation sciences. Part I: Polysaccharide and cyclodextrin selectors","volume":"120","author":"Scriba","year":"2019","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Scriba, G.K.E. (2019). Chiral Separations, Springer.","DOI":"10.1007\/978-1-4939-9438-0"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"13235","DOI":"10.1021\/acs.chemrev.1c00846","article-title":"Recognition in the domain of molecular chirality: From noncovalent interactions to separation of enantiomers","volume":"122","author":"Peluso","year":"2022","journal-title":"Chem. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Mangelings, D., Eeltink, S., and Vander Heyden, Y. (2020). Recent developments in liquid and supercritical fluid chromatographic enantioseparations. Handbook of Analytical Separations, Elsevier.","DOI":"10.1016\/B978-0-444-64070-3.00009-6"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/s41570-023-00476-z","article-title":"Detection and analysis of chiral molecules as disease biomarkers","volume":"7","author":"Liu","year":"2023","journal-title":"Nat. Rev. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/j.chroma.2009.10.022","article-title":"Chiral recognition by enantioselective liquid chromatography: Mechanisms and modern chiral stationary phases","volume":"1217","year":"2010","journal-title":"J. Chromatogr. A"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"116332","DOI":"10.1016\/j.trac.2021.116332","article-title":"Application of enantioselective separation techniques to bioanalysis of chiral drugs and their metabolites","volume":"143","author":"Chankvetadze","year":"2021","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1002\/chir.10004","article-title":"Direct chiral separation of unnatural amino acids by high-performance liquid chromatography on a ristocetin A-bonded stationary phase","volume":"13","author":"Armstrong","year":"2001","journal-title":"Chirality"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0021-9673(00)00917-1","article-title":"High-performance liquid chromatographic separation of enantiomers of synthetic amino acids on a ristocetin A chiral stationary phase","volume":"904","author":"Armstrong","year":"2000","journal-title":"J. Chromatogr. A"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S0021-9673(97)00938-2","article-title":"High-performance liquid chromatographic separation of enantiomers of unusual amino acids on a teicoplanin chiral stationary phase","volume":"793","author":"Armstrong","year":"1998","journal-title":"J. Chromatogr. A"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"17063","DOI":"10.1021\/acs.analchem.2c03042","article-title":"Comprehensive online reversed-phase \u00d7 chiral two-dimensional liquid chromatography-mass spectrometry with data-independent sequential window acquisition of all theoretical fragment-ion spectra-acquisition for untargeted enantioselective amino acid analysi","volume":"94","author":"Karongo","year":"2022","journal-title":"Anal. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e2300351","DOI":"10.1002\/jssc.202300351","article-title":"Comprehensive reversed-phase\u00d7chiral two-dimensional liquid chromatography coupled to quadrupole-time-of-flight tandem mass spectrometry with post-first dimension flow splitting for untargeted enantioselective amino acid analysis","volume":"46","author":"Karongo","year":"2023","journal-title":"J. Sep. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"338858","DOI":"10.1016\/j.aca.2021.338858","article-title":"Enantioselective multiple heart cutting online two-dimensional liquid chromatography-mass spectrometry of all proteinogenic amino acids with second dimension chiral separations in one-minute time scales on a chiral tandem column","volume":"1180","author":"Karongo","year":"2021","journal-title":"Anal. Chim. Acta"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1021\/acs.analchem.3c05426","article-title":"Three-minute enantioselective amino acid analysis by ultra-high-performance liquid chromatography drift tube ion mobility-mass spectrometry using a chiral core\u2013shell tandem column approach","volume":"96","author":"Jaag","year":"2024","journal-title":"Anal. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jpba.2018.06.045","article-title":"Liquid chromatographic enantiomer separations applying chiral ion-exchangers based on Cinchona alkaloids","volume":"159","author":"Ilisz","year":"2018","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1002\/elps.202300278","article-title":"Development of an easy-to-set-up multiple heart-cutting achiral\u2013chiral LC\u2013LC method for the analysis of branched-chain amino acids in commercial tablets","volume":"45","author":"Varfaj","year":"2024","journal-title":"Electrophoresis"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"342791","DOI":"10.1016\/j.aca.2024.342791","article-title":"A journey in unraveling the enantiorecognition mechanism of 3,5-dinitrobenzoyl-amino acids with two Cinchona alkaloid-based chiral stationary phases: The power of molecular dynamic simulations","volume":"1314","author":"Varfaj","year":"2024","journal-title":"Anal. Chim. Acta"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1002\/1521-4168(20001101)23:11<628::AID-JHRC628>3.0.CO;2-2","article-title":"Direct high-performance liquid chromatographic enantioseparation of \u03b2-methyl-substituted unusual amino acids on a quinine-derived chiral anion-exchange stationary phase","volume":"23","author":"Lindner","year":"2000","journal-title":"J. High Resolut. Chromatogr."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Haynes, W.M., Lide, D.R., and Bruno, T.J. (2016). CRC Handbook of Chemistry and Physics, CRC Press.","DOI":"10.1201\/9781315380476"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0021-9673(01)90875-1","article-title":"Retention model for high-performance ion-exchange chromatography","volume":"266","author":"Kopaciewicz","year":"1983","journal-title":"J. Chromatogr. A"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0021-9673(93)83061-V","article-title":"Chiral ion-exchange chromatography. Correlation between solute retention and a theoretical ion-exchange model using imprinted polymers","volume":"654","author":"Sellergren","year":"1993","journal-title":"J. Chromatogr. A"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0021-9673(99)00176-4","article-title":"Retention models for ions in chromatography","volume":"855","year":"1999","journal-title":"J. Chromatogr. A"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.chroma.2016.05.040","article-title":"Enantioseparation of \u00df-carboline derivatives on polysaccharide- and strong cation exchanger-based chiral stationary phases. A comparative study","volume":"1467","author":"Megyesi","year":"2016","journal-title":"J. Chromatogr. A"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"462212","DOI":"10.1016\/j.chroma.2021.462212","article-title":"Unexpected effects of mobile phase solvents and additives on retention and resolution of N-acyl-D,L-leucine applying Cinchonane-based chiral ion exchangers","volume":"1648","author":"Orosz","year":"2021","journal-title":"J. Chromatogr. A"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.chroma.2016.05.041","article-title":"Combinatorial effects of the configuration of the cationic and the anionic chiral subunits of four zwitterionic chiral stationary phases leading to reversal of elution order of cyclic \u03b2-amino acid enantiomers as ampholytic model compounds","volume":"1467","author":"Ilisz","year":"2016","journal-title":"J. Chromatogr. A"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1002\/chir.23471","article-title":"Chiral separation of dipeptides on Cinchona-based zwitterionic chiral stationary phases under buffer-free reversed-phase conditions","volume":"34","author":"Asnin","year":"2022","journal-title":"Chirality"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1039\/a702403g","article-title":"Chromatography on chiral stationary phases","volume":"7","author":"Allenmark","year":"1997","journal-title":"J. Mater. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0021-9673(98)00781-X","article-title":"Comparison of two methods for the gas chromatographic determination of thermodynamic parameters of enantioselectivity","volume":"843","author":"Schurig","year":"1999","journal-title":"J. Chromatogr. A"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0021-9673(03)00846-X","article-title":"Effect of phase ratio on van\u2019t Hoff analysis in reversed-phase liquid chromatography, and phase-ratio-independent estimation of transfer enthalpy","volume":"1003","author":"Chester","year":"2003","journal-title":"J. Chromatogr. A"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1002\/jssc.201701264","article-title":"Van\u2019t Hoff analysis in chiral chromatography","volume":"41","author":"Asnin","year":"2018","journal-title":"J. Sep. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"461371","DOI":"10.1016\/j.chroma.2020.461371","article-title":"Enantioselective retention mechanisms of dipeptides on antibiotic-based chiral stationary phases. II. Effect of the methanol content in the mobile phase","volume":"1626","author":"Asnin","year":"2020","journal-title":"J. Chromatogr. A"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2826","DOI":"10.1002\/jssc.201300559","article-title":"Click chemistry immobilization strategies in the development of strong cation exchanger chiral stationary phases for HPLC","volume":"36","author":"Wolrab","year":"2013","journal-title":"J. Sep. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jpba.2016.02.043","article-title":"Mechanistic considerations of enantiorecognition on novel Cinchona alkaloid-based zwitterionic chiral stationary phases from the aspect of the separation of trans-paroxetine enantiomers as model compounds","volume":"124","author":"Kohout","year":"2016","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/j.chroma.2008.12.045","article-title":"Stationary phase-related investigations of quinine-based zwitterionic chiral stationary phases operated in anion-, cation-, and zwitterion-exchange modes","volume":"1216","author":"Hoffmann","year":"2009","journal-title":"J. Chromatogr. A"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1021\/jm0310028","article-title":"Structure-activity study on the Phe side chain arrangement of endomorphins using conformationally constrained analogues","volume":"47","author":"Biyashev","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5167","DOI":"10.1021\/jm981011u","article-title":"Side chain methyl substitution in the \u03b4-opioid receptor antagonist TIPP has an important effect on the activity profile","volume":"41","author":"Mannekens","year":"1998","journal-title":"J. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1021\/jm060721u","article-title":"\u03b2-Methyl substitution of cyclohexylalanine in Dmt-Tic-Cha-Phe peptides results in highly potent \u03b4 opioid antagonists","volume":"50","author":"Ioja","year":"2007","journal-title":"J. Med. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1021\/jo00239a036","article-title":"A short and efficient synthesis of (3S,4S)-4-[(tert-Butyloxycarbonyl)amino]-5-cyclohexyl-3-hydroxypentanoic acid ethyl ester","volume":"53","author":"Schuda","year":"1988","journal-title":"J. Org. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5784","DOI":"10.1021\/acs.orglett.5b02895","article-title":"Chiral pyridoxal-catalyzed asymmetric biomimetic transamination of \u03b1-keto acids","volume":"17","author":"Shi","year":"2015","journal-title":"Org. Lett."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/9\/4004\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:20:26Z","timestamp":1760030426000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/9\/4004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,23]]},"references-count":57,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["ijms26094004"],"URL":"https:\/\/doi.org\/10.3390\/ijms26094004","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,23]]}}}