Article
Chemistry, Multidisciplinary
Takayuki Katoh, Hiroaki Suga
Summary: The study demonstrates the feasibility of multiple and consecutive incorporations of alpha-aminoxy/alpha-hydrazino acids with different configurations into peptides during ribosomal translation, including macrocyclic peptide scaffolds.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Physical
Le-Cheng Wang, Xiao-Feng Wu
Summary: In this study, we have developed an unprecedented and general method for the direct synthesis of various alpha-amino acid derivatives by activating inert C-H bonds. By introducing an appropriate electron-withdrawing group, we successfully modulated the nucleophilicity and polarity of the reaction, resulting in a broad substrate scope and excellent tolerance of sensitive functional groups in this catalytic strategy.
JOURNAL OF CATALYSIS
(2023)
Article
Chemistry, Organic
Jian-Ting Sun, Xin Li, Tian-Yu Yang, Min Lv, Ling-Yan Chen, Bang-Guo Wei
Summary: A practical method for synthesizing alpha-aminophosphonates through catalysis has been developed, resulting in the successful synthesis of the desired compounds.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Organic
Soo Min Cho, Jae Yeon Kim, Shinyeong Han, Do Hyun Ryu
Summary: This study describes the development of a visible light-mediated synthetic method for chiral 1,2-amino tertiary alcohols. By using a chiral oxazaborolidinium ion catalyst and photosensitizer, the enantioselective addition of an alpha-aminoalkyl radical to aryl methyl ketones under visible light leads to chiral 1,2-amino tertiary alcohol derivatives in high yields and excellent enantioselectivities.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Dominik Reich, Adam Noble, Varinder K. Aggarwal
Summary: Amino phosphonates are highly effective inhibitors in various biological processes due to their unique structural and electronic properties. They find numerous applications as enzyme inhibitors, herbicides, antiviral, antibacterial, and antifungal agents. This study presents a novel and convenient method utilizing visible-light organophotocatalysis to convert activated derivatives of alpha-amino acids directly into their respective alpha-amino phosphonate counterparts, demonstrating broad applicability, mild reaction conditions, and successful late-stage functionalization of drug molecules.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Soo Min Cho, Jae Yeon Kim, Shinyeong Han, Do Hyun Ryu
Summary: A visible light-mediated synthetic method for chiral 1,2-amino tertiary alcohols has been developed, involving the enantioselective addition of an alpha-aminoalkyl radical to aryl methyl ketones under visible light with the presence of a chiral oxazaborolidinium ion catalyst and photosensitizer. The reaction provides chiral 1,2-amino tertiary alcohol derivatives in high yields (up to 88%) with excellent enantioselectivities (up to 98% ee). Mechanistic studies suggest a plausible catalytic cycle.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Bo Li, Jie Zhang, Li Li, Gong Chen
Summary: A practical method for chiroptical sensing of free alpha amino acids has been developed, utilizing a three-component labeling reaction to derivatize analytes into an isoindole for sensitive CD and UV readouts. The assay shows high selectivity and accuracy across a wide range of concentrations, with a unprecedented lower limit of 10 micromolar concentration.
Article
Biotechnology & Applied Microbiology
Jing Zhang, Manyu Liang, Lijuan Wu, Yanhong Yang, Yingjie Sun, Qin Wang, Xiaowei Gao
Summary: This study developed a simple and cost-effective method to digest feathers using Bacillus licheniformis WHU, yielding a hydrolysate that can be directly used as a bioactive nutrient resource. In addition, supplementation with feather hydrolysate had positive effects on intestinal health, immune function, and microbial composition in mice.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Masoumeh Rajabihashjin, Mehrshad Zeinalabedini, Ali Asghari, Mohammad Reza Ghaffari, Ghasem Hosseini Salekdeh
Summary: This study investigated the effects of environmental variables on yield related traits and metabolite contents of Persian fenugreeks. Multivariate statistical techniques were applied to determine important proxy variables and establish a relevant model for predicting bioactive compounds in fenugreeks. The results showed that temperature and solar irradiation were key variables in 4-hydroxyisoleucine accumulation, while seed weight and the precursor of isoleucine predicted trigonelline content. These findings provide valuable information for the breeding strategies of this multipurpose crop.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Organic
Alejandro Torregrosa-Chinillach, Asier Carral-Menoyo, Enrique Gomez-Bengoa, Rafael Chinchilla
Summary: A highly efficient enantioselective alpha-nitrogenation method has been developed for synthesizing alpha,alpha-disubstituted alpha-nitrogenated aldehydes without the need for any solvents, achieving high yields and excellent enantioselectivities. The sustainability and rationality of the method have been demonstrated through green metrics calculation and theoretical calculations.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Marina Kurbasic, Ana M. Garcia, Simone Viada, Silvia Marchesan
Summary: The study focused on the catalytic effects of bioactive hydrogels based on tripeptide self-assembly, specifically exploring the impact of modifications on the hydrogel and esterase mimicry activity.
The synthesis and characterization of three analogues with terminal modifications were analyzed, and their self-assembly, hydrogelation, and esterase-like biocatalysis were tested through various techniques.
These findings offer valuable insights into how chemical modifications affect the self-assembly of biocatalytic hydrogels and can potentially aid in the design of supramolecular catalysts for enhanced performance in the future.
Article
Chemistry, Organic
Joomyung Jun, Ronald T. Raines
Summary: The synthesis of alpha-aryl-alpha-diazoamides was achieved through a two-step process involving Pd-catalyzed C-H arylation and aminolysis, enabling the esterification of carboxyl groups in aqueous solution to become substrates for an esterase. This broad synthetic route paves the way for further development of diazo compounds in chemical biology.
Article
Chemistry, Organic
Gangarajulu Kesavulu, Biguvu Balachandra, Kavirayani R. Prasad
Summary: The use of lithio tris(methylthio)methane as an anion equivalent enables the synthesis of α-amino acids. Reactions with nonracemic sulfinimines yield α-sulfinamido trithioformates with excellent diastereoselectivity. Conversion of trithioformates to diverse functionalities such as α-amino acid thioesters, esters, anilides, amides, and di/tripeptides is achieved without epimerization of chiral centers.
Article
Chemistry, Multidisciplinary
Aibo Li, Xinjian Song, Qiao Ren, Peiwang Bao, Xinyu Long, Fuli Huang, Lvjiang Yuan, Jianrong Steve Zhou, Xurong Qin
Summary: A cobalt-catalyzed deuteration of amidoacrylates using deuterated methanol resulted in the synthesis of highly enantioselective α,β-dideuterio-α-amino esters with almost complete deuteration (99%). This new protocol was successfully employed for the preparation of dideuterio-α-amino acid fragments in certain drugs, and also applied in the concise synthesis of dideuterio L-DOPA.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Caria Evans, William J. Berkey, Christopher W. Jones, Stefan France
Summary: A Zr-catalyzed synthesis of tetrasubstituted 1,3-diacylpyrroles has been reported using N-acyl alpha-aminoaldehydes and 1,3-dicarbonyl compounds. The reaction showed high yields (up to 88%) and the products were found to be hydrolytically and configurationally stable. The N-acyl alpha-aminoaldehydes were easily prepared from corresponding alpha-amino acids. The reaction could accommodate various substrate types and a range of 1,3-dicarbonyls, including aldehyde derived from a l,l-dipeptide, an in situ generated aldehyde, and an N-acylated glucosamine.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Oncology
Zheqi Li, Yang Wu, Megan E. Yates, Nilgun Tasdemir, Amir Bahreini, Jian Chen, Kevin M. Levine, Nolan M. Priedigkeit, Azadeh Nasrazadani, Simak Ali, Laki Buluwela, Spencer Arnesen, Jason Gertz, Jennifer K. Richer, Benjamin Troness, Dorraya El-Ashry, Qiang Zhang, Lorenzo Gerratana, Youbin Zhang, Massimo Cristofanilli, Maritza A. Montanez, Prithu Sundd, Callen T. Wallace, Simon C. Watkins, Caterina Fumagalli, Elena Guerini-Rocco, Li Zhu, George C. Tseng, Nikhil Wagle, Jason S. Carroll, Paul Jank, Carsten Denkert, Maria M. Karsten, Jens-Uwe Blohmer, Ben H. Park, Peter C. Lucas, Jennifer M. Atkinson, Adrian Lee, Steffi Oesterreich
Summary: This study demonstrated the potential role of ESR1 mutations in distant recurrence of breast cancer. Through transcriptomic profiling and functional experiments, it was shown that ESR1 mutations altered the cell adhesive gene network, leading to enhanced cell-cell contacts and decreased cell-extracellular matrix adhesion. Additionally, ESR1-mutant cells formed larger and more compact multicellular circulating tumor cell clusters in vivo, and ESR1 mutations were associated with enrichment of circulating tumor cell clusters in metastatic breast cancer patients.
Article
Biochemistry & Molecular Biology
Simon C. Baker, Andrew S. Mason, Raphael G. Slip, Katie T. Skinner, Andrew Macdonald, Omar Masood, Reuben S. Harris, Tim R. Fenton, Manikandan Periyasamy, Simak Ali, Jennifer Southgate
Summary: Limited understanding of bladder cancer aetiopathology hampers progress in reducing incidence. This study provides missing mechanistic evidence linking reactivated BKPyV-infection to bladder cancer risk.
Meeting Abstract
Oncology
Sacha J. Howell, Laura M. Kenny, Simon Lord, Matthew G. Krebs, Tobias Arkenau, Richard Baird, Iain R. MacPherson, Ash Bahl, Glen Clack, Edward Ainscow, Anthony G. M. Barrett, Paul A. Dickinson, Matthew J. Fuchter, Manfred Lehnert, Simak Ali, Stuart McIntosh, Charles Coombes
Meeting Abstract
Oncology
Zheqi Li, Yang Wu, Olivia Mcginn, Amir Bahreini, Nolan M. Priedigkeit, Kai Ding, Sayali Onkar, Carol A. Sartorius, Lori Miller, Margaret Rosenzweig, Nikhil Wagle, Jennifer K. Richer, William J. Muller, Laki Buluwela, Simak Ali, Dario A. A. Vignali, Yusi Fang, Li Zhu, George C. Tseng, Jason Gertz, Jennifer M. Atkinson, Adrian V. Lee, Steffi Oesterreich
Article
Multidisciplinary Sciences
Zheqi Li, Olivia McGinn, Yang Wu, Amir Bahreini, Nolan M. Priedigkeit, Kai Ding, Sayali Onkar, Caleb Lampenfeld, Carol A. Sartorius, Lori Miller, Margaret Rosenzweig, Ofir Cohen, Nikhil Wagle, Jennifer K. Richer, William J. Muller, Laki Buluwela, Simak Ali, Tullia C. Bruno, Dario A. A. Vignali, Yusi Fang, Li Zhu, George C. Tseng, Jason Gertz, Jennifer M. Atkinson, Adrian Lee, Steffi Oesterreich
Summary: Mutations in ESR1 gene are associated with acquired resistance to therapy in luminal breast cancer. ESR1 mutant tumors gain basal-like features and show increased expression of basal cytokeratines and immune activation. These mutations are linked to intrinsic subtype switching and may be targeted for immune therapeutic vulnerabilities.
NATURE COMMUNICATIONS
(2022)
Correction
Multidisciplinary Sciences
R. C. Coombes, P. D. Badman, J. P. Lozano-Kuehne, X. Liu, I. R. Macpherson, I. Zubairi, R. D. Baird, N. Rosenfeld, J. Garcia-Corbacho, N. Cresti, R. Plummer, A. Armstrong, R. Allerton, D. Landers, H. Nicholas, L. McLellan, A. Lim, F. Mouliere, O. E. Pardo, V. Ferguson, M. J. Seckl
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Theodora A. Constantin, Anabel Varela-Carver, Kyle K. Greenland, Gilberto Serrano de Almeida, Ellen Olden, Lucy Penfold, Simon Ang, Alice Ormrod, Damien A. Leach, Chun-Fui Lai, Edward K. Ainscow, Ash K. Bahl, David Carling, Matthew J. Fuchter, Simak Ali, Charlotte L. Bevan
Summary: This study demonstrates that the CDK7 inhibitor CT7001 selectively inhibits proliferation and cell cycle in prostate cancer cells, and exerts antitumor effects by activating p53, inducing apoptosis, and suppressing transcription mediated by full-length and constitutively active AR splice variants. Oral administration of CT7001 suppresses the growth of CRPC xenografts, and significantly enhances the growth inhibition achieved by enzalutamide. Transcriptome analyses indicate that the mode of action of CT7001 in vivo is through inhibition of the cell cycle and AR function.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Lubaid Saleh, Penelope D. Ottewell, Janet E. Brown, Steve L. Wood, Nichola J. Brown, Caroline Wilson, Catherine Park, Simak Ali, Ingunn Holen
Summary: CDK4/6 inhibitor palbociclib significantly impedes tumour growth in murine models of both estrogen receptor positive and triple negative bone metastatic breast cancer when given daily. However, tumour cells become insensitive to palbociclib after a treatment break, and the levels of key proteins may play a role in this.
Correction
Multidisciplinary Sciences
R. C. Coombes, Sacha Howell, Simon R. Lord, Laura Kenny, Janine Mansi, Zahi Mitri, Carlo Palmieri, Linnea I. Chap, Paul Richards, William Gradishar, Sagar Sardesai, Jason Melear, Joyce O'Shaughnessy, Patrick Ward, Pavani Chalasani, Tobias Arkenau, Richard D. Baird, Rinath Jeselsohn, Simak Ali, Glen Clack, Ashwani Bahl, Stuart McIntosh, Matthew G. Krebs
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
R. Charles Coombes, Sacha Howell, Simon R. Lord, Laura Kenny, Janine Mansi, Zahi Mitri, Carlo Palmieri, Linnea I. Chap, Paul Richards, William Gradishar, Sagar Sardesai, Jason Melear, Joyce O'Shaughnessy, Patrick Ward, Pavani Chalasani, Tobias Arkenau, Richard D. Baird, Rinath Jeselsohn, Simak Ali, Glen Clack, Ashwani Bahl, Stuart McIntosh, Matthew G. Krebs
Summary: This study reports the clinical trial results of samuraciclib as an anti-cancer treatment, showing its clinical activity in patients with triple negative breast cancer and HR+/HER2- breast cancer.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Ebtihal H. Mustafa, Geraldine Laven-Law, Zoya Kikhtyak, Van Nguyen, Simak Ali, Alex A. Pace, Richard Iggo, Alemwork Kebede, Ben Noll, Shudong Wang, Jean M. Winter, Amy R. Dwyer, Wayne D. Tilley, Theresa E. Hickey
Summary: Targeting transcription via CDK9 could be a potential therapeutic strategy for TNBC. Preclinical studies showed that a selective CDK9 inhibitor, CDDD11-8, effectively inhibited proliferation, induced cell cycle arrest, and increased apoptosis of TNBC cells in vitro and in vivo, without apparent toxicity to normal tissues.
Article
Oncology
Anisha Ramessur, Bana Ambasager, Iker Valle Aramburu, Freddie Peakman, Kelly Gleason, Christoph Lehmann, Venizelos Papayannopoulos, Raoul Charles Coombes, Ilaria Malanchi
Summary: An elevated number of circulating neutrophils is a poor prognostic factor for breast cancer, and bone marrow activation is found to be involved. However, it is unclear how early this activation can be detected. In this study, we found subtype-specific changes in circulating neutrophils and perturbations in their overall kinase activity in newly diagnosed breast cancer patients. Different subtypes of breast cancer patients exhibited distinct neutrophil kinase activity patterns, and the lifespan of neutrophils also increased in cancer patients. These results suggest that the kinase activation patterns in circulating neutrophils may be used as markers to differentiate cancer patients from those with benign breast lesions.
BREAST CANCER RESEARCH
(2023)
Meeting Abstract
Chemistry, Multidisciplinary
Basil Greber, Victoria Cushing, Junjie Feng, Adrian Koh, Abhay Kotecha, Matthew Fuchter, Simak Ali
ACTA CRYSTALLOGRAPHICA A-FOUNDATION AND ADVANCES
(2022)
