David A Gallegos1, Josep Saurí2, Ryan D Cohen3, Xuemei Wan1, Patrick Videau4, Alec O Vallota-Eastman1, Lamiaa A Shaala5, Diaa T A Youssef6, R Thomas Williamson3, Gary E Martin3, Benjamin Philmus1, Aleksandra E Sikora1, Jane E Ishmael1, Kerry L McPhail1. 1. Department of Pharmaceutical Sciences, College of Pharmacy , Oregon State University , Corvallis , Oregon 97331 , United States. 2. Structure Elucidation Group, Process and Analytical Research and Development , Merck & Co., Inc. , 33 Avenue Louis Pasteur , Boston , Massachusetts 02115 , United States. 3. Structure Elucidation Group, Process and Analytical Research and Development , Merck & Co., Inc. , 126 East Lincoln Avenue , Rahway , New Jersey 07065 , United States. 4. Department of Biology, College of Arts and Sciences , Dakota State University , Madison , South Dakota 57042 , United States. 5. Suez Canal University Hospital, Suez Canal University , Ismailia 41522 , Egypt. 6. Department of Natural Products, Faculty of Pharmacy , King Abdulaziz University , Jeddah 21589 , Saudi Arabia.
Abstract
Jizanpeptins A-E (1-5) are micropeptin depsipeptides isolated from a Red Sea specimen of a Symploca sp. cyanobacterium. The planar structures of the jizanpeptins were established using NMR spectroscopy and mass spectrometry and contain 3-amino-6-hydroxy-2-piperidone (Ahp) as one of eight residues in a typical micropeptin motif, as well as a side chain terminal glyceric acid sulfate moiety. The absolute configurations of the jizanpeptins were assigned using a combination of Marfey's methodology and chiral-phase HPLC analysis of hydrolysis products compared to commercial and synthesized standards. Jizanpeptins A-E showed specific inhibition of the serine protease trypsin (IC50 = 72 nM to 1 μM) compared to chymotrypsin (IC50 = 1.4 to >10 μM) in vitro and were not overtly cytotoxic to HeLa cervical or NCI-H460 lung cancer cell lines at micromolar concentrations.
Jizanpeptins A-E (1-5) are n class="Chemical">micropeptin depsipeptides isolated from a Red Sea specimen of a Symploca sp. cyanobacterium. The planar structures of the jizanpeptins were established using NMR spectroscopy and mass spectrometry and contain 3-amino-6-hydroxy-2-piperidone (Ahp) as one of eight residues in a typical micropeptin motif, as well as a side chain terminal glyceric acid sulfate moiety. The absolute configurations of the jizanpeptins were assigned using a combination of Marfey's methodology and chiral-phase HPLC analysis of hydrolysis products compared to commercial and synthesized standards. Jizanpeptins A-E showed specific inhibition of the serine protease trypsin (IC50 = 72 nM to 1 μM) compared to chymotrypsin (IC50 = 1.4 to >10 μM) in vitro and were not overtly cytotoxic to HeLa cervical or NCI-H460 lung cancer cell lines at micromolar concentrations.
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