72-18-4Relevant articles and documents
Structures and antitumor activities of ten new and twenty known surfactins from the deep-sea bacterium Limimaricola sp. SCSIO 53532
Chen, Min,Chen, Rouwen,Ding, Wenping,Li, Yanqun,Tian, Xinpeng,Yin, Hao,Zhang, Si
, (2022/01/11)
Surfactins are natural biosurfactants with myriad potential applications in the areas of healthcare and environment. However, surfactins were almost exclusively produced by the bacterium Bacillus species in previous reported literatures, together with difficulty in isolating pure monomer, which resulted in making extensive effort to remove duplication and little discovery of new surfactins in recent years. In the present study, the result of Molecular Networking indicated that Limimaricola sp. SCSIO 53532 might well be a potential resource for surfacin-like compounds based on OSMAC strategy. To search for new surfactins with significant biological activity, further study was undertaken on the strain. As a result, ten new surfactins (1–10), along with twenty known surfactins (11–30), were isolated from the ethyl acetate extract of SCSIO 53532. Their chemical structures were established by detailed 1D and 2D NMR spectroscopy, HRESIMS data, secondary ion mass spectrometry (MS/MS) analysis, and chemical degradation (Marfey's method) analysis. Cytotoxic activities of twenty-seven compounds against five human tumor cell lines were tested, and five compounds showed significant antitumor activities with IC50 values less than 10 μM. Furtherly, analysis of structure–activity relationships revealed that the branch of side chain, the esterification of Glu or Asp residue, and the amino acid residue of position 7 possessed a great influence on antitumor activity.
Enhanced carboxypeptidase efficacies and differentiation of peptide epimers
Sung, Yu-Sheng,Putman, Joshua,Du, Siqi,Armstrong, Daniel W.
, (2022/01/29)
Carboxypeptidases enzymatically cleave the peptide bond of C-terminal amino acids. In humans, it is involved in enzymatic synthesis and maturation of proteins and peptides. Carboxypeptidases A and Y have difficulty hydrolyzing the peptide bond of dipeptides and some other amino acid sequences. Early investigations into different N-blocking groups concluded that larger moieties increased substrate susceptibility to peptide bond hydrolysis with carboxypeptidases. This study conclusively demonstrates that 6-aminoquinoline-N-hydroxysuccimidyl carbamate (AQC) as an N-blocking group greatly enhances substrate hydrolysis with carboxypeptidase. AQC addition to the N-terminus of amino acids and peptides also improves chromatographic peak shapes and sensitivities via mass spectrometry detection. These enzymes have been used for amino acid sequence determination prior to the advent of modern proteomics. However, most modern proteomic methods assume that all peptides are comprised of L-amino acids and therefore cannot distinguish L-from D-amino acids within the peptide sequence. The majority of existing methods that allow for chiral differentiation either require synthetic standards or incur racemization in the process. This study highlights the resistance of D-amino acids within peptides to enzymatic hydrolysis by Carboxypeptidase Y. This stereoselectivity may be advantageous when screening for low abundance peptide stereoisomers.
Cyclic Tetrapeptides with Synergistic Antifungal Activity from the Fungus Aspergillus westerdijkiae Using LC-MS/MS-Based Molecular Networking
Chen, Baosong,Dai, Huanqin,Han, Junjie,Li, Erwei,Liu, Hongwei,Lyu, Zhitang,Song, Fuhang,Sun, Jingzu,Wang, Hanying,Wang, Tao,Wang, Wenzhao,Zhang, Rui
, (2022/02/17)
Fungal natural products play a prominent role in the development of pharmaceuticalagents. Two new cyclic tetrapeptides (CTPs), westertide A (1) and B (2), with eight known compounds (3-10) were isolated from the fungus Aspergillus westerdijkiae guided by
Direct monitoring of biocatalytic deacetylation of amino acid substrates by1H NMR reveals fine details of substrate specificity
De Cesare, Silvia,McKenna, Catherine A.,Mulholland, Nicholas,Murray, Lorna,Bella, Juraj,Campopiano, Dominic J.
supporting information, p. 4904 - 4909 (2021/06/16)
Amino acids are key synthetic building blocks that can be prepared in an enantiopure form by biocatalytic methods. We show that thel-selective ornithine deacetylase ArgE catalyses hydrolysis of a wide-range ofN-acyl-amino acid substrates. This activity was revealed by1H NMR spectroscopy that monitored the appearance of the well resolved signal of the acetate product. Furthermore, the assay was used to probe the subtle structural selectivity of the biocatalyst using a substrate that could adopt different rotameric conformations.
Inherently chiral dialkyloxy-calix[4]arene acetic acids as enantiodiscriminating additives for high-performance liquid chromatography separation of d,l-amino acids
Kalchenko, Olga I.,Trybrat, Oleksandr O.,Yesypenko, Oleksandr A.,Dyakonenko, Viktoriya V.,Shishkina, Svitlana V.,Kalchenko, Vitali I.
, p. 722 - 730 (2021/08/26)
Inherently chiral dialkyloxy-calix[4]arene acetic acids with asymmetric placement of substituents on the lower rim of the macrocycle were first studied as enantiodiscriminating additives to the mobile phase MeCN/H2O/HCOOH (75/25/0.02 by volume) in the high-performance liquid chromatography (HPLC) separation of d,l-alanine and d,l-valine on the achiral stationary phase ZORBAX Original CN. The dependence of enantio-binding properties on the position of alkyl groups is demonstrated. The highest resolution (1.65) and enantioselectivity (1.80) were obtained for the 1,2-dipropyloxy-calix[4]arene acetic acid.
Leveraging Peptaibol Biosynthetic Promiscuity for Next-Generation Antiplasmodial Therapeutics
Lee, Jin Woo,Collins, Jennifer E.,Wendt, Karen L.,Chakrabarti, Debopam,Cichewicz, Robert H.
supporting information, p. 503 - 517 (2021/03/01)
Malaria remains a worldwide threat, afflicting over 200 million people each year. The emergence of drug resistance against existing therapeutics threatens to destabilize global efforts aimed at controlling Plasmodium spp. parasites, which is expected to leave vast portions of humanity unprotected against the disease. To address this need, systematic testing of a fungal natural product extract library assembled through the University of Oklahoma Citizen Science Soil Collection Program has generated an initial set of bioactive extracts that exhibit potent antiplasmodial activity (EC50 25 μM, selectivity index > 250). The unique chemodiversity afforded by these fungal isolates serves to unlock new opportunities for translating peptaibols into a bioactive scaffold worthy of further development.
Argicyclamides A-C Unveil Enzymatic Basis for Guanidine Bis-prenylation
Balloo, Nandani,Fujita, Kei,Matsuda, Kenichi,Okino, Tatsufumi,Phan, Chin-Soon,Wakimoto, Toshiyuki
supporting information, p. 10083 - 10087 (2021/07/26)
Guanidine prenylation is an outstanding modification in alkaloid and peptide biosynthesis, but its enzymatic basis has remained elusive. We report the isolation of argicyclamides, a new class of cyanobactins with unique mono- and bis-prenylations on guanidine moieties, from Microcystis aeruginosa NIES-88. The genetic basis of argicyclamide biosynthesis was established by the heterologous expression and in vitro characterization of biosynthetic enzymes including AgcF, a new guanidine prenyltransferase. This study provides important insight into the biosynthesis of prenylated guanidines and offers a new toolkit for peptide modification.
Method for photolysis of amido bonds
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Paragraph 0046; 0048-0049; 0102-0105, (2021/06/26)
The invention discloses a method for photo-splitting amido bonds, wherein the method is mild in reaction condition and can realize splitting of amido bonds by using illumination. The method for photo-splitting the amido bonds comprises the following steps: reacting 2,4-dinitrofluorobenzene with an amino group of a substance which contains alpha amino acid at the tail end and is shown as a structural formula I to generate a compound 1 represented by a structural formula II; and under light irradiation, carrying out amido bond cleavage reaction on the compound 1, wherein R1 is a side chain group of alpha-amino acid, and R2 is aryl, aliphatic hydrocarbon, -CH(R)-COOH or polypeptide.
Powerful Steroid-Based Chiral Selector for High-Throughput Enantiomeric Separation of α-Amino Acids Utilizing Ion Mobility-Mass Spectrometry
Li, Yuling,Zhou, Bowen,Wang, Keke,Zhang, Jing,Sun, Wenjian,Zhang, Li,Guo, Yinlong
, p. 13589 - 13596 (2021/10/21)
Stereospecific recognition of amino acids (AAs) plays a crucial role in chiral biomarker-based diagnosis and prognosis. Separation of AA enantiomers is a long and tedious task due to the requirement of AA derivatization prior to the chromatographic or electrophoretic steps which are also time-consuming. Here, a mass-tagged chiral selector named [d0]/[d5]-estradiol-3-benzoate-17β-chloroformate ([d0]/[d5]-17β-EBC) with high reactivity and good enantiomeric resolution in regard to AAs was developed. After a quick and easy chemical derivatization step of AAs using 17β-EBC as the single chiral selector before ion mobility-mass spectrometry analysis, good enantiomer separation was achieved for 19 chiral proteinogenic AAs in a single analytical run (～2 s). A linear calibration curve of enantiomeric excess was also established using [d0]/[d5]-17β-EBC. It was demonstrated to be capable of determining enantiomeric ratios down to 0.5% in the nanomolar range. 17β-EBC was successfully applied to investigate the absolute configuration of AAs among peptide drugs and detect trace levels of-AAs in complex biological samples. These results indicated that [d0]/[d5]-17β-EBC may contribute to entail a valuable step forward in peptide drug quality control and discovering chiral disease biomarkers.
Isolation, Structure Determination, and Total Synthesis of Hoshinoamide C, an Antiparasitic Lipopeptide from the Marine Cyanobacterium Caldora penicillata
Iwasaki, Arihiro,Ohtomo, Keisuke,Kurisawa, Naoaki,Shiota, Ikuma,Rahmawati, Yulia,Jeelani, Ghulam,Nozaki, Tomoyoshi,Suenaga, Kiyotake
, p. 126 - 135 (2021/01/13)
Hoshinoamide C (1), an antiparasitic lipopeptide, was isolated from the marine cyanobacterium Caldora penicillata. Its planar structure was elucidated by spectral analyses, mainly 2D NMR, and the absolute configurations of the α-amino acid moieties were determined by degradation reactions followed by chiral-phase HPLC analyses. To clarify the absolute configuration of an unusual amino acid moiety, we synthesized two possible diastereomers of hoshinoamide C and determined its absolute configuration based on a comparison of their spectroscopic data with those of the natural compound. Hoshinoamide C (1) did not exhibit any cytotoxicity against HeLa or HL60 cells at 10 μM, but inhibited the growth of the parasites responsible for malaria (IC50 0.96 μM) and African sleeping sickness (IC50 2.9 μM).
