Review
Biochemistry & Molecular Biology
Tasha R. Davis, Mariah R. Pierce, Sadie X. Novak, James L. Hougland
Summary: Ghrelin is a peptide hormone that regulates hunger and metabolism through its unique acylation process; it is the only known hormone that directly stimulates appetite and hunger signaling. Research advancements in GOAT enzymology, structural modeling, and inhibitor development have enhanced our understanding of ghrelin signaling and offer potential for therapeutic applications.
Article
Endocrinology & Metabolism
Susanna Bianzano, Andrea Henrich, Lena Herich, Brigitte Kalsch, Donald Sarubbi, Friedeborg Seitz, Thomas Forst
Summary: Two Phase I studies showed that BI 1356225, a GOAT inhibitor, was well-tolerated in healthy males and subjects with overweight/obesity. However, treatment with BI 1356225 for 28 days did not lead to significant reduction in bodyweight or changes in appetite, eating control, or energy intake.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2023)
Review
Physiology
Mariah R. R. Pierce, James L. L. Hougland
Summary: Acylation modifications in biological processes and their association with various health conditions have attracted much research interest. The membrane bound O-acyltransferase (MBOAT) family of enzymes play a crucial role in these modifications. Recent advancements in solubilization approaches and structural characterization techniques have provided a wealth of information on the structure and function of MBOATs, enabling a better understanding of their catalytic activity and potential therapeutic applications.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Endocrinology & Metabolism
Jennifer L. Miller, Andre Lacroix, Lynne M. Bird, Ashley H. Shoemaker, Andrea Haqq, Cheri L. Deal, Kristie A. Clark, Michael H. Ames, Jeffrey G. Suico, Amparo de la Pena, Caroline Fortier
Summary: GLWL-01, a GOAT inhibitor, was evaluated for the treatment of PWS patients. The study showed that GLWL-01 effectively reduced the levels of AG and UAG, but did not significantly improve hyperphagia-related behavior or other clinical measures. The drug was well tolerated and safe.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Chemistry, Organic
Yupeng Cao, Haifeng Huang, Limin Wang, Xiangyang Lin, Jun Yang
Summary: In this study, the nitration of NH on the 1,2,3-triazole ring and the synthesis of nitrogen-rich energetic compounds were reported. A novel fused nitrogen-rich heterocycle was obtained, showing high nitrogen content and good thermal stability. The compounds synthesized exhibited high detonation velocity and detonation pressure.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Yupeng Cao, Haifeng Huang, Limin Wang, Xiangyang Lin, Jun Yang
Summary: In this study, the nitration of NH on the 1,2,3-triazole ring was reported, and several nitrogen-rich energetic compounds were synthesized based on the key intermediate 4-azido-5-(chlorodinitromethyl)-2-nitro-2H-1,2,3-triazole (5). Compound 5 was successfully constructed from 4-amino-1H-1,2,3-triazole-5-carbonitrile (1) through four steps. Furthermore, potassium 4-azido-5-(dinitromethyl)-2H-1,2,3-triazole (6), diammonium (8), and dihydrazinium (9) salts were synthesized and characterized. A novel fused nitrogen-rich heterocycle, 6H-[1,2,3]triazolo[4,5-d][1,2,3] triazine-6,7-diamine (10), with high nitrogen content and good thermal stability, as well as insensitivity to mechanical stimuli, was obtained.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Antonela S. Fittipaldi, Daniel Castrogiovanni, Daniela Lufrano, Camila Saenz, Pablo N. De Francesco, Tyler Lalonde, Leonard G. Luyt, Sonia Cantel, Jean -Alain Fehrentz, Maria F. Andreoli, Mario Perello
Summary: The aim of this study was to investigate the relationship between des-acylation and proteolysis of plasma ghrelin and its decrease after food intake or in individuals with obesity. The levels of ghrelin, desacyl-ghrelin (DAG), glucose, insulin, ghrelin des-acylation, and ghrelin proteolysis were assessed in plasma before and after a test meal in 40 participants. The results showed that ghrelin proteolysis was increased in males with obesity and after a meal in lean individuals.
Article
Biochemistry & Molecular Biology
Claire E. Coupland, T. Bertie Ansell, Mark S. P. Sansom, Christian Siebold
Summary: The membrane-bound O-acyltransferase (MBOAT) superfamily catalyses the transfer of acyl chains to substrates implicated in essential cellular functions. Aberrant function of MBOATs is associated with various diseases and MBOATs are promising drug targets. Recent progress in structural characterisation of MBOATs has advanced our understanding of their functional mechanism. Integration of information across the MBOAT family has identified a common MBOAT fold and provided insights into substrate and inhibitor engagement. Further studies should focus on characterising MBOATs within their membrane environment as lipid-associated proteins.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Article
Chemistry, Organic
Linlin Wang, Kuan Chen, Zilong Wang, Yang Yi, Meng Zhang, Aobulikasimu Hasan, Yi Kuang, Sharpkate Shaker, Rong Yu, Haotian Wang, Haiyang Liu, Min Ye, Xue Qiao
Summary: A highly regio- and stereo-specific acetyltransferase, AmAT19, was discovered from Astragalus membranaceus, which could selectively catalyze the 6 alpha-OH acetylation of tetracyclic triterpenes and steroids. The acetylated products showed increased inhibitory activity against SARS-CoV-2, suggesting AmAT19 as a promising catalyst for enhancing the bioactivities of these molecules and expanding their diversity.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Xuewu Sui, Kun Wang, Kangkang Song, Chen Xu, Jiunn Song, Chia-Wei Lee, Maofu Liao, Robert V. Farese, Tobias C. Walther
Summary: This study reports the structures of inhibitors of the triacylglycerol synthesis enzyme. The inhibitors were found to block the enzyme's activity by either blocking the entrance of the substrate binding tunnel or interacting with the catalytic residues. Furthermore, the inhibitors showed minimal activity against related enzymes, but a single-residue mutation increased their inhibitory effect.
NATURE COMMUNICATIONS
(2023)
Review
Pharmacology & Pharmacy
Emanuela Micioni Di Bonaventura, Luca Botticelli, Fabio Del Bello, Gianfabio Giorgioni, Alessandro Piergentili, Wilma Quaglia, Carlo Cifani, Maria Vittoria Micioni Di Bonaventura
Summary: Ghrelin is a potent regulator of food intake and obesity, with its functions mediated by interactions with receptors in the hypothalamic area. The two forms of ghrelin have contrasting effects on body weight and eating behaviors, and also impact the urge to eat under stressful conditions.
PHARMACOLOGICAL RESEARCH
(2021)
Review
Chemistry, Applied
Farid Ahmed, Hai Xiong
Summary: This review summarizes the latest developments in chemosensors based on click generated triazoles for a range of metal cations, anions, and neutral analytes, highlighting the need for continuous research accumulation in this rapidly growing field to meet demand.
Article
Biochemistry & Molecular Biology
Oriol Bosch-Sanz, Yvette Rabada, Xevi Biarnes, Javier Pedreno, Luis Caveda, Mercedes Balcells, Jordi Martorell, David Sanchez-Garcia
Summary: Fibrinolysis is a natural process that removes fibrin deposits to ensure blood fluidity. Excessive fibrinolytic activity can cause complications in surgery or trauma. Current antifibrinolytic drugs require high doses and have side effects, limiting their use in patients with renal impairment. This study synthesized a series of compounds and identified a candidate with higher specificity and lower dosage. Molecular docking and dynamics analysis revealed the importance of 1,2,3-triazole in the activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Physical
Parveen Saini, Gurjaspreet Singh, Gurpreet Kaur, Jandeep Singh, Harminder Singh
Summary: This report describes the absorbance response of a molecular assembly incorporating o-Cresolphthalein appended 1,4-disubstituted 1,2,3-triazole (o-CPT) upon complexation with Pb(II) ions. A Copper (I) catalyzed alkyne-azide cycloaddition reaction was employed to fabricate the designed receptor, which was characterized through various spectroscopic techniques. The results highlight the high sensitivity and selectivity of the receptor towards Pb(II) ions.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Chemistry, Medicinal
Daniels Jelisejevs, Anna Lina Bula, Linda Kinena
Summary: The study investigates /q- and y-lactams as electrophilic warheads for covalently targeting the Mpro active site at Cys145. The highest inhibitory activity was achieved using a pyrazolidinone warhead attached to the targeting dipeptide. Notably, the synergy between the warhead and the targeting dipeptide is crucial for the successful inhibition of Mpro.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biochemistry & Molecular Biology
Melanie J. Blanden, Kiall F. Suazo, Emily R. Hildebrandt, Daniel S. Hardgrove, Meet Patel, William P. Saunders, Mark D. Distefano, Walter K. Schmidt, James L. Hougland
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Review
Biochemistry & Molecular Biology
James L. Hougland
BIOCHEMICAL SOCIETY TRANSACTIONS
(2019)
Article
Biochemical Research Methods
Nan Wang, Alice L. Pilo, Feifei Zhao, Jiexun Bu, Scott A. McLuckey
RAPID COMMUNICATIONS IN MASS SPECTROMETRY
(2018)
Article
Biochemistry & Molecular Biology
Maria B. Campana, Flaviyan Jerome Irudayanathan, Tasha R. Davis, Kayleigh R. McGovern-Gooch, Rosemary Loftus, Mohammad Ashkar, Najae Escoffery, Melissa Navarro, Michelle A. Sieburg, Shikha Nangia, James L. Hougland
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Review
Endocrinology & Metabolism
Alfonso Abizaid, James L. Hougland
TRENDS IN ENDOCRINOLOGY AND METABOLISM
(2020)
Article
Biochemistry & Molecular Biology
Sudhat Ashok, Emily R. Hildebrandt, Colby S. Ruiz, Daniel S. Hardgrove, David W. Coreno, Walter K. Schmidt, James L. Hougland
Article
Chemistry, Multidisciplinary
Shanti Swaroop Srivastava, Joseph E. Darling, Jimmy Suryadi, James C. Morris, Mark E. Drew, Sriram Subramaniam
Review
Chemistry, Medicinal
Jacob E. Moose, Katelyn A. Leets, Nilamber A. Mate, John D. Chisholm, James L. Hougland
EXPERT OPINION ON THERAPEUTIC PATENTS
(2020)
Article
Biochemistry & Molecular Biology
Sara L. Deschaine, Mehdi Farokhnia, Adriana Gregory-Flores, Lia J. Zallar, Zhi-Bing You, Hui Sun, Deon M. Harvey, Renata C. N. Marchette, Brendan J. Tunstall, Bharath K. Mani, Jacob E. Moose, Mary R. Lee, Eliot Gardner, Fatemeh Akhlaghi, Marisa Roberto, James L. Hougland, Jeffrey M. Zigman, George F. Koob, Leandro F. Vendruscolo, Lorenzo Leggio
Summary: Alcohol decreases ghrelin levels in both rats and humans, but this decrease is not in proportion to alcohol's caloric value or through direct interaction with the ghrelin system.
Review
Biochemistry & Molecular Biology
Tasha R. Davis, Mariah R. Pierce, Sadie X. Novak, James L. Hougland
Summary: Ghrelin is a peptide hormone that regulates hunger and metabolism through its unique acylation process; it is the only known hormone that directly stimulates appetite and hunger signaling. Research advancements in GOAT enzymology, structural modeling, and inhibitor development have enhanced our understanding of ghrelin signaling and offer potential for therapeutic applications.
Article
Biochemistry & Molecular Biology
Garrett L. Schey, Peter H. Buttery, Emily R. Hildebrandt, Sadie X. Novak, Walter K. Schmidt, James L. Hougland, Mark D. Distefano
Summary: A new systematic approach combining solid-phase peptide synthesis and mass spectrometric analysis has been developed to discover novel peptide substrates for FTase. Experimental results show that this method successfully identifies multiple substrates for FTase, with some even surpassing the benchmark sequence CMIIM in efficiency.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Johannes Morstein, Taysir Bader, Ariana L. Cardillo, Julian Schackmann, Sudhat Ashok, James L. Hougland, Christine A. Hrycyna, Dirk H. Trauner, Mark D. Distefano
Summary: This study describes the development of photoswitchable analogs of an isoprenoid lipid and evaluates their potential for optically controlling the isoprenylation processing pathway. The results show that the analog effectively controls substrate prenylation but has minimal impact on subsequent processing steps.
ACS CHEMICAL BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Sara L. Deschaine, Morten A. Hedegaard, Claire L. Pince, Mehdi Farokhnia, Jacob E. Moose, Ingrid A. Stock, Sravani Adusumalli, Fatemeh Akhlaghi, James L. Hougland, Agnieszka Sulima, Kenner C. Rice, George F. Koob, Leandro F. Vendruscolo, Birgitte Holst, Lorenzo Leggio
Summary: The metabolite PF-6870961 of PF-5190457 has been identified as a potential treatment for alcohol use disorder. It shows binding affinity and inverse agonist activity at GHSR1a, and can suppress food intake in rats through GHSR receptor-mediated pathways.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2023)
Article
Nanoscience & Nanotechnology
Md. Shahadat Hossain, Zhe Zhang, Sudhat Ashok, Ashley R. Jenks, Christopher J. Lynch, James L. Hougland, Davoud Mozhdehi
Summary: This study genetically engineered prokaryotes to develop a simple and high-yield biosynthetic route for producing farnesylated proteins. They revealed the determinants of their material properties and this could contribute to the development of farnesylated proteins as recombinant therapeutics or biomaterials with programmable assembly.
ACS APPLIED BIO MATERIALS
(2022)
Article
Chemistry, Multidisciplinary
Yiao Wang, Ozgun Kilic, Clifford M. Csizmar, Sudhat Ashok, James L. Hougland, Mark D. Distefano, Carston R. Wagner
Summary: Multicellular biology relies on the control of cell-cell interactions, which can be manipulated using a multivalent lipidated scaffold. Chemically self-assembled nanorings (CSANs) can target specific cellular antigens, offering a unique platform for studying cell-cell interactions and T cell-mediated cytotoxicity. Antigen-targeted prenylated CSANs provide a general approach for regulating specific cell-cell interactions with applications in both fundamental research and therapeutics.
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
