Article
Chemistry, Medicinal
Tingting Fan, Boqiang Liang, Lingling Nie, Juan Wang, Huijun Zhang, Aaron Ciechanover, Yan Xu, Jing An, Ziwei Huang
Summary: The interaction between EphB4 and EFNB2 plays a crucial role in cancer by controlling bidirectional signaling that affects tumor growth and angiogenesis. In this study, researchers designed a bivalent ligand that showed higher binding affinity to EphB4 and successfully inhibited cancer cell motility and tube formation.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Paul M. Levine, Timothy W. Craven, Xinting Li, Aaron T. Balana, Gregory H. Bird, Marina Godes, Patrick J. Salveson, Patrick W. Erickson, Mila Lamb, Maggie Ahlrichs, Michael Murphy, Cassandra Ogohara, Meerit Y. Said, Loren D. Walensky, Matthew R. Pratt, David Baker
Summary: Peptide and protein bioconjugation technologies have revolutionized the ability to install functional groups at specific sites. This study introduces a site-specific bioconjugation strategy inspired by chemical ligation at serine, utilizing a noncanonical amino acid to create analogues of Semaglutide. The analogues show improved potency and stability, demonstrating the potential of serine ligation for generating stabilized peptide therapeutics.
ACS CHEMICAL BIOLOGY
(2022)
Article
Nanoscience & Nanotechnology
Fang-Chu Lin, Qilin Yu, Jeffrey Zink
Summary: This self-contained nanocapsule utilizes an esterase and an alternating magnetic field to achieve nonspecific cytotoxic anticancer drug delivery and release. In vivo experiments demonstrated excellent biocompatibility and high tumor-targeting/inhibiting efficiency, with the esterase efficiently cleaving ester bonds for enhanced anticancer efficacy.
ACS APPLIED NANO MATERIALS
(2021)
Article
Chemistry, Medicinal
Carine M. Abdelmalek, Zexi Hu, Thales Kronenberger, Jenni Kublbeck, Franziska J. M. Kinnen, Salma S. Hesse, Afsin Malik, Mark Kudolo, Raimund Niess, Matthias Gehringer, Lars Zender, Paula A. Witt-Enderby, Darius P. Zlotos, Stefan A. Laufer
Summary: Anticancer drug conjugates that simultaneously target two receptors may overcome the limitations of current cancer treatments. A series of compounds connecting tamoxifen or endoxifen with the EGFR-inhibitor gefitinib exhibit potent anticancer activity in breast cancer cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
M. Rodriguez-Rios, G. Rinaldi, A. Megia-Fernandez, A. Lilienkampf, C. T. Robb, A. G. Rossi, M. Bradley
Summary: In this study, a near infrared probe based on FRET technology was developed for specific detection of human neutrophil elastase. The probe selectively detects activated neutrophils and can label neutrophil extracellular traps.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
M. Rodriguez-Rios, G. Rinaldi, A. Megia-Fernandez, A. Lilienkampf, C. T. Robb, A. G. Rossi, M. Bradley
Summary: We describe a FRET-based, tri-branched near infrared probe for specific detection of human neutrophil elastase. The probe enables selective detection of activated neutrophils and labeling of neutrophil extracellular traps. It emits in the NIR region with minimal interference from endogenous biomolecules and autofluorescence.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Ying Yun, Chenlu Zhang, Shimeng Guo, Xiaoying Liang, Yuan Lan, Min Wang, Ning Zhuo, Jianpeng Yin, Huanan Liu, Min Gu, Jing Li, Xin Xie, Fajun Nan
Summary: A new series of betulinic acid derivatives were identified as potent TGR5 agonists which showed species difference in activity, and a key amino acid H88 (Y89) was found to contribute to the species difference. Introducing the mTGR5 (H88Y) mutation in mice resulted in significant glucose-lowering effects and stimulated GLP-1 and insulin secretion, highlighting the potential for further investigation of TGR5 agonists.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Computer Science, Interdisciplinary Applications
Fatemeh Sabzian-Molaei, Mohammad Amin Ahmadi, Zahra Nikfarjam, Mohammad Sabzian-Molaei
Summary: This study aimed to design mutant peptides that could block the interaction between gp120 and the CD4 receptor on host cells, thus preventing HIV-1 infection. Three peptides showed potential as HIV inhibitors.
MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING
(2023)
Article
Chemistry, Medicinal
Himalaya Singh, Annaram Thirupathi, Bishwaprava Das, Manojkumar Janni, Renu Kumari, Sandeep Singh, Mamunur Rashid, Mohammad Wahajuddin, Musuvathi Motilal Balamurali, Kumaravelu Jagavelu, Saravanan Peruncheralathan
Summary: The study demonstrates that 2,3-ACBTs inhibit angiogenesis by regulating the Akt/Src signaling pathway and disrupting cytoskeletal filaments of endothelial cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Maanvee Mirakhur, Martin Diener
Summary: Proteinases released during inflammatory or allergic responses affect gastrointestinal functions via proteinase-activated receptors. This study focuses on the effect of PAR1 and PAR2 agonists on electrogenic ion transport, tissue conductance, and muscle contractility in different segments of the gastrointestinal tract. The results suggest that the functions of PAR1 and PAR2 vary depending on the intestinal segment.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Carlo Baggio, Anna Kulinich, Cassandra N. Dennys, Rochelle Rodrigo, Kathrin Meyer, Iryna Ethell, Maurizio Pellecchia
Summary: The study utilized an innovative NMR-guided screening and ligand design approach to derive low-molecular-weight ligands capable of mimicking interactions elicited by ephrin ligands. These agents demonstrated nanomolar affinity, activated receptors in cellular assays with motor neurons, and provided significant motor neuron protection from ALS patient-derived astrocytes. Structural studies on the complex between the ligand-binding domain and the most active agent offered insights into the agents' mechanism at a molecular level, forming a strong foundation for potential treatment of ALS and other human diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Garima Dixit, Willow Schanz, Benjamin A. Pappas, Thorsten Maretzky
Summary: Metalloproteases ADAM10 and ADAM17 have been identified as differentially regulated FGFR membrane sheddases, playing roles in modulating FGFR signaling during cell migration. Ectodomain shedding can impact the function of ligand-induced FGFR signaling in cell movement.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Arundhasa Chandrabalan, Rithwik Ramachandran
Summary: Proteinase-activated receptors (PARs) in prostate cancer cells regulate tumor growth and metastasis through autocrine signaling. In this study, PAR1 and PAR2 were found to be functional in PC3 cells, while PAR4 was not expressed. The secretion of proteolytic enzymes by PC3 cells triggers cleavage of PARs, leading to autocrine signaling and the regulation of genes related to prostate cancer. PAR1 deficiency promotes cell migration and suppresses cell proliferation, while PAR2 deficiency has the opposite effects.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Medicine, Research & Experimental
Adam P. Curnock, Giovanna Bossi, Jyothi Kumaran, Lindsay J. Bawden, Rita Figueiredo, Rajeevkumar Tawar, Katherine Wiseman, Emma Henderson, Sec Julie Hoong, Veronica Gonzalez, Hemza Ghadbane, David Eo Knight, Ronan O'Dwyer, David X. Overton, Christina M. Lucato, Nicola Mg Smith, Carlos R. Reis, Keith Page, Lorraine M. Whaley, Michelle L. McCully, Stephen Hearty, Tara M. Mahon, Peter Weber
Summary: The study developed PD-1 agonist ImmTAAI molecules that can inhibit T cell function by mimicking the action of PD-L1. These molecules specifically bind to target cells and effectively activate the PD-1 receptor on interacting T cells, achieving immune suppression.
Article
Pharmacology & Pharmacy
George Leonidis, Anastasia Koukiali, Ioanna Sigala, Katerina Tsimaratou, Dimitris Beis, Thomas Giannakouros, Eleni Nikolakaki, Vasiliki Sarli
Summary: This study presents the optimized synthesis of JH-VII-139-1 and its c(RGDyK) peptide conjugates, and investigates their chemostability, cytotoxic and antiangiogenic properties. Most conjugates retained mid nanomolar-level inhibitory activity against SRPK1 kinase, and two conjugates showed antiproliferative effects against multiple cancer cells. In vivo zebrafish screening assays demonstrated the ability of the synthesized conjugates to inhibit intersegmental vessels. Additionally, flow cytometry experiments revealed receptor-mediated endocytosis of the conjugates in specific cancer cells.
Article
Peripheral Vascular Disease
Alfred C. Aplin, Roberto F. Nicosia
Review
Peripheral Vascular Disease
Patrycja Nowak-Sliwinska, Kari Alitalo, Elizabeth Allen, Andrey Anisimov, Alfred C. Aplin, Robert Auerbach, Hellmut G. Augustin, David O. Bates, Judy R. van Beijnum, R. Hugh F. Bender, Gabriele Bergers, Andreas Bikfalvi, Joyce Bischoff, Barbara C. Boeck, Peter C. Brooks, Federico Bussolino, Bertan Cakir, Peter Carmeliet, Daniel Castranova, Anca M. Cimpean, Ondine Cleaver, George Coukos, George E. Davis, Michele De Palma, Anna Dimberg, Ruud P. M. Dings, Valentin Djonov, Andrew C. Dudley, Neil P. Dufton, Sarah-Maria Fendt, Napoleone Ferrara, Marcus Fruttiger, Dai Fukumura, Bart Ghesquiere, Yan Gong, Robert J. Griffin, Adrian L. Harris, Christopher C. W. Hughes, Nan W. Hultgren, M. Luisa Iruela-Arispe, Melita Irving, Rakesh K. Jain, Raghu Kalluri, Joanna Kalucka, Robert S. Kerbel, Jan Kitajewski, Ingeborg Klaassen, Hynda K. Kleinmann, Pieter Koolwijk, Elisabeth Kuczynski, Brenda R. Kwak, Koen Marien, Juan M. Melero-Martin, Lance L. Munn, Roberto F. Nicosia, Agnes Noel, Jussi Nurro, Anna-Karin Olsson, Tatiana V. Petrova, Kristian Pietras, Roberto Pili, Jeffrey W. Pollard, Mark J. Post, Paul H. A. Quax, Gabriel A. Rabinovich, Marius Raica, Anna M. Randi, Domenico Ribatti, Curzio Ruegg, Reinier O. Schlingemann, Stefan Schulte-Merker, Lois E. H. Smith, Jonathan W. Song, Steven A. Stacker, Jimmy Stalin, Amber N. Stratman, Maureen Van de Velde, Victor W. M. van Hinsbergh, Peter B. Vermeulen, Johannes Waltenberger, Brant M. Weinstein, Hong Xin, Bahar Yetkin-Arik, Seppo Yla-Herttuala, Mervin C. Yoder, Arjan W. Griffioen
Article
Cell Biology
A. C. Aplin, W. H. Zhu, E. Fogel, R. F. Nicosia
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2009)
Article
Peripheral Vascular Disease
Alfred C. Aplin, Eric Fogel, Roberto F. Nicosia
Article
Peripheral Vascular Disease
Alfred C. Aplin, Giovanni Ligresti, Eric Fogel, Penelope Zorzi, Kelly Smith, Roberto F. Nicosia
Article
Hematology
James A. Stefater, Sujata Rao, Katie Bezold, Alfred C. Aplin, Roberto F. Nicosia, Jeffrey W. Pollard, Napoleone Ferrara, Richard A. Lang
Review
Pharmacology & Pharmacy
Zhao Ming (David) Dong, Alfred C. Aplin, Roberto F. Nicosia
CURRENT PHARMACEUTICAL DESIGN
(2009)
Article
Developmental Biology
Roberto F. Nicosia, Penelope Zorzi, Giovanni Ligresti, Ann Morishita, Alfred C. Aplin
INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY
(2011)
Article
Immunology
Maurizio Gelati, Alfred C. Aplin, Eric Fogel, Kelly D. Smith, Roberto F. Nicosia
JOURNAL OF IMMUNOLOGY
(2008)
Article
Cell Biology
Penelope Zorzi, Alfred C. Aplin, Kelly D. Smith, Roberto F. Nicosia
JOURNAL OF LEUKOCYTE BIOLOGY
(2010)
Article
Multidisciplinary Sciences
Giovanni Ligresti, Alfred C. Aplin, Bruce E. Dunn, Ann Morishita, Roberto F. Nicosia
Article
Peripheral Vascular Disease
Alfred C. Aplin, Roberto F. Nicosia
Article
Endocrinology & Metabolism
Joseph J. Castillo, Alfred C. Aplin, Daryl J. Hackney, Meghan F. Hogan, Nathalie Esser, Andrew T. Templin, Rehana Akter, Steven E. Kahn, Daniel P. Raleigh, Sakeneh Zraika, Rebecca L. Hull
Summary: The study found that aggregation of IAPP is toxic to islet endothelial cells and induces inflammatory responses, resulting in decreased capillary density, increased capillary diameter, and an increased number of pericytes.
Article
Engineering, Biomedical
Lan T. H. Dang, Takahide Aburatani, Graham A. Marsh, Bryce G. Johnson, Stella Alimperti, Christine J. Yoon, Angela Huang, Suzanne Szak, Naoki Nakagawa, Ivan Gomez, Shuyu Ren, Sarah K. Read, Chris Sparages, Alfred C. Aplin, Roberto F. Nicosia, Chris Chen, Giovanni Ligresti, Jeremy S. Duffield