Simultaneous enantiomeric analysis is especially important for medicine, food security, and life science. Chiral analysis of multicomponent amine mixtures still faces many challenges. Here, our work demonstrates for the first time that a novel chiral derivatizing agent CDApro based on trans-4-fluoro-l-proline (trans4Fpro) has been successfully used for the rapid simultaneous analysis of 22 chiral nonamino acid (non-AA) amines, multicomponent l/d-AAs, or mirror-image dipeptides in a mixture, as well as amines with chiral centers several carbons remote to the amino group. Furthermore, determination of enantiomeric purity and quantification of chiral amines can be made using CDApro, which serves as a robust and powerful reagent for the differentiation of multicomponent chiral amines.

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α‐Conotoxins are small disulfide‐rich peptides found in the venom of marine cone snails and are potent antagonists of nicotinic acetylcholine receptors (nAChRs). They are valuable pharmacological tools and have potential therapeutic applications for the treatment of chronic pain or neurological diseases and disorders. In the present study, we synthesized and functionally characterized a novel α‐conotoxin Bt1.8, which was cloned from Conus betulinus. Bt1.8 selectively inhibited ACh‐evoked currents in Xenopus oocytes expressing rat(r) α6/α3β2β3 and rα3β2 nAChRs with an IC50 of 2.1 nM and 9.4 nM, respectively, and similar potency for human (h) α6/α3β2β3 and hα3β2 nAChRs. Additionally, Bt1.8 had higher binding affinity with a slower dissociation rate for the rα6/α3β2β3 subtype compared to rα3β2. The amino acid sequence of Bt1.8 is significantly different from other reported α‐conotoxins targeting the two nAChR subtypes. Further Alanine scanning analyses demonstrated that residues Ile9, Leu10, Asn11, Asn12 and Asn14 are critical for its inhibitory activity at the α6/α3β2β3 and α3β2 subtypes. Moreover, the NMR structure of Bt1.8 indicated the presence of a relatively larger hydrophobic zone than other α4/7‐conotoxins which may explain its potent inhibition at α6/α3β2β3 nAChRs.

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