Inherent susceptibility of peptides to enzymatic degradation in the gastrointestinal tract is a key bottleneck in oral peptide drug development. Here, we present a systematic analysis of (i) the gut stability of disulfide-rich peptide scaffolds, orally administered peptide therapeutics, and well-known neuropeptides and (ii) medicinal chemistry strategies to improve peptide gut stability. Among a broad range of studied peptides, cyclotides were the only scaffold class to resist gastrointestinal degradation, even when grafted with non-native sequences. Backbone cyclization, a frequently applied strategy, failed to improve stability in intestinal fluid, but several site-specific alterations proved efficient. This work furthermore highlights the importance of standardized gut stability test conditions and suggests defined protocols to facilitate cross-study comparison. Together, our results provide a comparative overview and framework for the chemical engineering of gut-stable peptides, which should be valuable for the development of orally administered peptide therapeutics and molecular probes targeting receptors within the gastrointestinal tract.

Structural and pharmacological study of parallel, antiparallel and N- to C-terminal cyclized homo- and heterodimers of vasopressin and oxytocin. This study spotlights dimerization as a strategy to modulate the pharmacology of neuropeptides.

We report a novel and efficient strategy for the preparation of the high-value triterpenoid betulinic acid based on extraction and streamlined oxidation of betulin from the industrial by-product birch bark. The initial extraction of betulin relies on a biphasic system and allowed extracting betulin in short times at room temperature. The crude extract could be directly oxidized, thereby providing a chromium-free, time-and energy saving strategy for the manufacturing of betulinic acid in high yield. † Electronic supplementary information (ESI) available: Additional graphs and data on extraction and oxidation experiments, copies of NMR spectra for isolated betulin and betulinic acid. See

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The tricyclic core in the title compound, C26H34O4Si2, shows disorder of the furan ring and deviates slightly from planarity, with the largest displacement from the least-squares plane [0.166 (2) Å] for the major disordered part of the methine C atom. To this C atom the likewise disordered vinyl group is attached, lying nearly perpendicular to the tricyclic core. In the crystal, mutual C—H...π interactions between the methine group of the furan ring and the central ring of the tricyclic core of an adjacent molecule lead to inversion-related dimers.