A Self‐Assembled Oligopeptide as a Versatile NMR Alignment Medium for the Measurement of Residual Dipolar Couplings in Methanol

Abstract

Residual dipolar coupling (RDC) is a powerful structural parameter for the determination of the constitution, conformation, and configuration of organic molecules. Herein, we report the first liquid crystal-based orienting medium that is compatible with MeOH, thus enabling RDC acquisitions of a wide range of intermediate to polar organic molecules. The liquid crystals were produced from self-assembled oligopeptide nanotubes (AAKLVFF), which are stable at very low concentrations. The presented alignment medium is highly homogeneous, and the size of RDCs can be scaled with the concentration of the peptide. To assess the accuracy of the RDC measurement by employing this new medium, seven bioactive natural products from different classes were chosen and analyzed. The straightforward preparation of the anisotropic alignment sample will offer a versatile and robust protocol for the routine RDC measurement of natural products.

Heterologous Expression of a VioA Variant Activates Cryptic Compounds in a Marine-Derived Brevibacterium Strain

“…The HR-ESIMS analysis disclosed that the molecular formulas of 1 , 2 , 4 and 5 were C 9 H 7 NO, C 10 H 9 NO 2 , C 19 H 16 N 2 O 2 and C 11 H 8 O 2 with molecular ion peaks at m / z 146.0598 [M + H] + , 176.0706 [M + H] + , 303.1132 [M − H] − and 173.1170 [M + H] + , respectively ( Figures S10, S15, S17 and S22 ). The structures of 1 , 2 , 4 and 5 were determined by NMR data assignment and comparison with the reported literatures [ 16 , 17 , 18 , 19 ], which were identified as indole-3-carboxaldehyde, indole-3-acetic acid, 2-(1 H -indol-3-ylmethyl)-1 H -indole-3-acetic acid, and 2-methyl-1,4-naphthalenedione, respectively ( Figure 1 ). The 1 H and 13 C NMR chemical shift values of 1 , 2 , 4 and 5 are listed in Tables S1–S4 .…”

Residual Dipolar Couplings in Structure Determination of Natural Products

“…The self-assembled oligopeptide has the sequence of AAKLVFF, which was derived from a fragment of the amyloid β-peptide, afterward, we have successfully developed this liquid crystal-forming AAKLVFF peptide as a versatile alignment medium. This work was also the first example of a MeOH-based lyotropic liquid crystalline as an aligning medium at very low concentration, and seven natural products containing very different functional groups were measured to demonstrate the wide compatibility and applicability for the RDC analysis of natural products [ 22 ].…”

“… PMMA/CDCl 3 2017 Relative configuration [ 94 ] β-Heptapeptide β-HXaa PVAc/CD 3 OD 2017 Relative configuration [ 95 ] Gibberellin Gibberella fujikuroi AAKLVFF/CD 3 OD 2017 Absolute configuration [ 22 ] Ingenol Croton tiglium L. AAKLVFF/CD 3 OD 2017 Absolute configuration [ 22 ] Ginkgolide B Ginkgo biloba AAKLVFF/CD 3 OD 2017 Absolute configuration [ 22 ] Actinomycin D streptomyces sp. AAKLVFF/CD 3 OD 2017 Absolute configuration [ 22 ] Artemether Artemisia AAKLVFF/CD 3 OD 2017 Absolute configuration [ 22 ] Caulamidine A Calibugula intermis p-HEMA/CD 3 CN 2018 Absolute configuration [ 96 ]

Fig. 9 Natural product with the stereochemistry assigned by RDC measurements

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Cromolyn/gelatin mixtures as aqueous alignment media and utilization of their mechanical stability for a layering technique

“…These methods require a weak alignment of molecules dissolved within anisotropic matrices. Suitable alignment media are either liquid crystals (LCs) that show large magnetic anisotropies and consequentially orient in strong magnetic fields or cross‐linked polymeric gels forming uniaxial environments upon mechanical deformation. The LC approach allows fast sample‐preparation and several tailor‐made features such as switchable alignment based on concentration or temperature .…”