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1. Unambiguous Stereochemical Assignment of Cyclo(Phe-Pro), Cyclo(Leu-Pro), and Cyclo(Val-Pro) by Electronic Circular Dichroic Spectroscopy

   https://doi.org/10.3390/molecules26195981  

   Domzalski, Alison; Margent, Liliana; Vigo, Valeria; Dewan, Faizunnahar; Pilarsetty, Naga Vara; Xu, Yujia; Kawamura, Akira (October 2021, Molecules)

   2,5-diketopiperazines (DKPs) are cyclic dipeptides ubiquitously found in nature. In particular, cyclo(Phe-Pro), cyclo(Leu-Pro), and cyclo(Val-Pro) are frequently detected in many microbial cultures. Each of these DKPs has four possible stereoisomers due to the presence of two chirality centers. However, absolute configurations of natural DKPs are often ambiguous due to the lack of a simple, sensitive, and reproducible method for stereochemical assignment. This is an important problem because stereochemistry is a key determinant of biological activity. Here, we report a synthetic DKP library containing all stereoisomers of cyclo(Phe-Pro), cyclo(Leu-Pro), and cyclo(Val-Pro). The library was subjected to spectroscopic characterization using mass spectrometry, NMR, and electronic circular dichroism (ECD). It turned out that ECD can clearly differentiate DKP stereoisomers. Thus, our ECD dataset can serve as a reference for unambiguous stereochemical assignment of cyclo(Phe-Pro), cyclo(Leu-Pro), and cyclo(Val-Pro) samples from natural sources. The DKP library was also subjected to a biological screening using assays for E. coli growth and biofilm formation, which revealed distinct biological effects of cyclo(D-Phe-L-Pro). 

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2. Cyclo-Tetrakis(μ-diphenylphosphido)-1,5-bis(tri-tert-butylphosphine)-Tetracopper

   https://doi.org/10.3390/M1334  

   Dannenberg, Steven G.; Waterman, Rory (March 2022, Molbank)

   Copper phosphido compound Cu4(μ-PPh2)4(PtBu3)2 was synthesized by three synthetic methods and structurally characterized by X-ray diffraction and 1H, 31P, 13C and 31P HMBC NMR spectroscopy. Cu4(μ-PPh2)4(PtBu3)2 was also demonstrated to be a hydrophosphination pre-catalyst. 

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3. Chemical Reduction of a Nanosized [6]Cyclo‐2,7‐naphthylene Macrocycle

   https://doi.org/10.1002/anie.202100942  

   Zhou, Zheng; Wei, Zheng; Ikemoto, Koki; Sato, Sota; Isobe, Hiroyuki; Petrukhina, Marina A. (May 2021, Angewandte Chemie International Edition)

   null (Ed.)
4. Characterization of the cyclic dipeptide cyclo(His-Pro) in Arabidopsis

   https://doi.org/10.1093/plphys/kiaf174  

   Minen, Romina_I; Camalle, Maria_Dolores; Schwertfeger, Tyler_J; Abdulhakim, Fatimah; Reish, Hannah; Perez_de_Souza, Leonardo; Moreno, Juan_C; Schilmiller, Anthony; Thirumalaikumar, Venkatesh_P; Agarwal, Pallavi; et al (May 2025, Plant Physiology)

   Abstract Diketopiperazines (DKPs) are chemically and functionally diverse cyclic dipeptides associated primarily with microbes. Few DKPs have been reported from plants and animals; the best characterized is cyclo(His-Pro), found in the mammalian central nervous system, where it arises from the proteolytic cleavage of a thyrotropin-releasing tripeptide hormone. Herein, we report the identification of cyclo(His-Pro) in Arabidopsis (Arabidopsis thaliana), where its levels increase upon abiotic stress conditions, including high salt, heat, and cold. To screen for potential protein targets, we used isothermal shift assays, which examine changes in protein-melting stability upon ligand binding. Among the identified proteins, we focused on the glycolytic enzyme, cytosolic glyceraldehyde-3-phosphate dehydrogenase (GAPC1). Binding between the GAPC1 protein and cyclo(His-Pro) was validated using nano-differential scanning fluorimetry and microscale thermophoresis, and we could further demonstrate that cyclo(His-Pro) inhibits GAPC1 activity with an IC50 of ∼200 μm. This inhibition was conserved in human GAPDH. Inhibition of glyceraldehyde-3-phosphate dehydrogenase activity has previously been reported to reroute carbon from glycolysis toward the pentose phosphate pathway. Accordingly, cyclo(His-Pro) supplementation augmented NADPH levels, increasing the NADPH/NADP+ ratio. Phenotypic screening revealed that plants supplemented with cyclo(His-Pro) were more tolerant to high-salt stress, as manifested by higher biomass, which we show is dependent on GAPC1/2. Our work reports the identification and functional characterization of cyclo(His-Pro) as a modulator of glyceraldehyde-3-phosphate dehydrogenase in plants. 

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5. Trapping of Small Molecules within Single or Double Cyclo[18]carbon Rings

   https://doi.org/10.3390/molecules28052157  

   Trzęsowska, Natasza; Wysokiński, Rafał; Michalczyk, Mariusz; Zierkiewicz, Wiktor; Scheiner, Steve (March 2023, Molecules)

   The encapsulation of a set of small molecules, H2, CO, CO2, SO2, and SO3, by a circular C18 ring is investigated by quantum calculations. These ligands lie near the center of the ring but, with the exception of H2, are disposed roughly perpendicular to the ring plane. Their binding energies with the C18 vary from 1.5 kcal/mol for H2 up to 5.7 kcal/mol for SO2, and the bonding is dominated by dispersive interactions spread over the entire ring. The binding of these ligands on the outside of the ring is weaker but allows the opportunity for each to bond covalently with the ring. A pair of C18 units lie parallel to one another. This pair can bind each of these ligands in the area between them with only small perturbations of the double ring geometry. The binding energies of these ligands to this double ring configuration are amplified by some 50% compared to the single ring systems. The presented data concerning the trapping of small molecules may have larger implications regarding hydrogen storage or air pollution reduction. 

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