Article
Biotechnology & Applied Microbiology
Mingyang Li, Wei Shi, Jia Yang, Qi Wang, Haiyan Dong, Jun Chen, Lifang Zhang, Shanli Zhu
Summary: The MOMP-targeted affibody molecule (Z(MOMP):461) screened in this study showed the ability to recognize native MOMP in cells infected with C. trachomatis, indicating great potential for delivering drugs for target therapy.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Siyuan Song, Qinghong Shi
Summary: The outbreak of COVID-19 has led to an urgent need for advanced diagnosis and vaccination globally. The discovery of high-affinity ligands is crucial for the production of vaccines and diagnostic reagents. This study introduced a virtual library for screening ZRBD affibody ligands that target the receptor binding domain of the spike protein. Through molecular docking and dynamics simulations, three potential ZRBD affibodies were identified and their high affinity for RBD binding was confirmed.
Article
Chemistry, Multidisciplinary
Elena Shanina, Sakonwan Kuhaudomlarp, Eike Siebs, Felix F. Fuchsberger, Maxime Denis, Priscila da Silva Figueiredo Celestino Gomes, Mads H. Clausen, Peter H. Seeberger, Didier Rognan, Alexander Titz, Anne Imberty, Christoph Rademacher
Summary: Carbohydrate-protein interactions are crucial for cell-cell and host-pathogen recognition. This study identifies metal-binding pharmacophores as novel scaffolds for inhibiting Ca2+-dependent carbohydrate-protein interactions, addressing the challenge posed by the hydrophilic nature of these interactions.
COMMUNICATIONS CHEMISTRY
(2022)
Article
Cell Biology
Jinshun Zhu, Saidu Kamara, Qi Wang, Yanru Guo, Qingfeng Li, Linlin Wang, Jingjing Chen, Qianqian Du, Wangqi Du, Shao Chen, Shanli Zhu, Jun Chen, Maoping Chu, Lifang Zhang
Summary: This study identified three novel HPV16 E6-binding affibody molecules, which showed high binding affinity and specificity for HPV16 E6, selectively reducing the viability and proliferation of HPV16-positive cells. The combination of these affibody molecules with another targeting HPV16 E7 resulted in a more potent inhibition of cell proliferation, primarily through the induction of cell apoptosis and senescence. These findings suggest a potential rational strategy for molecular imaging and targeted therapy in HPV16-positive preneoplastic and neoplastic lesions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Fakhrossadat Emami, Ramesh Duwa, Asmita Banstola, Seon Min Woo, Taeg Kyu Kwon, Simmyung Yook
Summary: Dual-receptor targeted (DRT) nanoparticles with two distinct targeting agents were prepared for the delivery of docetaxel (DTX) to EGFR and PD-L1 positive cancer cells. The DRT-DTX-PLGA nanoparticles exhibited high cytotoxicity and enhanced apoptotic cell death compared to single ligand-targeted nanoparticles. The dual receptor mediated endocytosis of DRT-DTX-PLGA resulted in high intracellular DTX concentration and cytotoxic properties. DRT nanoparticles have the potential to improve cancer therapy by providing selectivity over single-ligand-targeted nanoparticles.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Chemistry, Medicinal
Illimar Hugo Rekand, Ruth Brenk
Summary: DrugPred_RNA is a structure-based druggability predictor developed to identify druggable RNA binding sites. The method performed well in discriminating druggable from less druggable protein binding sites and can contribute to direct drug discovery efforts for RNA targets. This predictor is robust against conformational and sequence changes in the binding sites, enhancing confidence in its performance.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Ali Alhuseinalkhudhur, Henrik Lindman, Per Liss, Tora Sundin, Fredrik Y. Frejd, Johan Hartman, Victor Iyer, Joachim Feldwisch, Mark Lubberink, Caroline Ronnlund, Vladimir Tolmachev, Irina Velikyan, Jens Sorensen
Summary: This study evaluated the predictive ability of imaging using the human epidermal growth factor receptor 2 (HER2)-binding tracer Ga-68-labeled Z(HER2:2891)-Cys-MMA-DOTA on the treatment response of patients with HER2-positive breast cancer. The results showed that [Ga-68]Ga-ABY-025 PET/CT can predict early metabolic response, but metabolic response is attenuated in recurrent disease.
JOURNAL OF NUCLEAR MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Silvia Salerno, Elisabetta Barresi, Emma Baglini, Valeria Poggetti, Sabrina Taliani, Federico Da Settimo
Summary: G-quadruplex (G4)-targeting compounds and Topo inhibitors are promising strategies to target tumor cells.
Simultaneous stabilization of G4 and inhibition of Topos can enhance antiproliferative activity and overcome cellular insensitivity and resistance.
Some chemotypes with dual activity and interesting pharmacological profile have been identified, but research in this field is still limited.
Article
Chemistry, Medicinal
Jie Cui, Yukimatsu Toh, Soohyun Park, Wangsheng Yu, Jianghua Tu, Ling Wu, Li Li, Joan Jacob, Sheng Pan, Kendra S. Carmon, Qingyun J. Liu
Summary: LGR4-6 are related receptors commonly upregulated in gastrointestinal cancers, with LGR5 being enriched in cancer stem cells. Targeting all three LGRs simultaneously is proposed for a more effective anti-tumor approach. A drug conjugate comprising an RSPO4 mutant and IgG1-Fc showed potent cytotoxic effects on cancer cells expressing any LGR, suppressing tumor growth without adverse effects.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Yan Li, Zhe Zhang, Renxiao Wang
Summary: This study presents an improved version of the empirical method HydraMap, called HydraMap v.2, which utilizes statistical potentials to predict hydration sites and compute desolvation energy during protein-ligand binding. The statistical potentials for protein-water interactions were updated based on crystal protein structures, and new potentials derived from solvated structures of small organic molecules were introduced to evaluate ligand-water interactions. HydraMap v.2 successfully predicts and compares hydration sites in a binding pocket before and after ligand binding, identifying key water molecules involved in the binding process. It also demonstrates good correlation between desolvation energies and ligand binding affinities in six target proteins, providing a cost-effective solution for estimating desolvation energy and guiding lead optimization in structure-based drug discovery.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Multidisciplinary
Rodrigo Aguayo-Ortiz, Laura Dominguez
Summary: Dinitroaniline derivatives are widely used as herbicides and exhibit good antiparasitic activity against protozoan parasites. Oryzalin, a representative dinitroaniline derivative, inhibits the growth of Toxoplasma gondii by binding selectively to alpha-tubulin and inhibiting microtubule polymerization.
Article
Chemistry, Medicinal
Sarah B. Krueger, Steven C. Zimmerman
Summary: This study reports a target-guided screening method based on dynamic covalent chemistry for identifying multitarget inhibitors. A library of amine- or aldehyde-containing fragments was synthesized and assembled, resulting in a diverse set of hit combinations. These hit combinations selectively and cooperatively inhibited transcription of myotonic dystrophy type 1 and Huntington's disease repeat sequences in vitro.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Daniel J. Rubins, Xiangjun Meng, Paul McQuade, Michael Klimas, Krista Getty, Shu-An Lin, Brett M. Connolly, Stacey S. O'Malley, Hyking Haley, Mona Purcell, Liza Gantert, Marie Holahan, Joel Lindgren, Par Eklund, Caroline Ekblad, Fredrik Y. Frejd, Eric D. Hostetler, Dinko E. Gonzalez Trotter, Jeffrey L. Evelhoch
Summary: In this study, the affinity-matured Affibody molecule Z(PD-L1_4) was evaluated for PET imaging of PD-L1 expression in tumors. Results showed that both PET tracers had significantly higher accumulation in PD-L1-expressing tumors compared to non-expressing tumors, indicating promising potential for clinical PD-L1 PET imaging with [F-18]AlF-NOTA-Z(PD-L1_4) and [Ga-68]NOTA-Z(PD-L1_4).
MOLECULAR IMAGING AND BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Yunjiang Zhou, Yunting Zou, Mei Yang, Shuang Mei, Xiaohao Liu, Huiyun Han, Chang-Dong Zhang, Miao-Miao Niu
Summary: This study demonstrates that a cyclic D-peptide NKTP-3, targeting both NRP1 and KRAS(G12D), could be a potential chemotherapeutic agent for KRAS(G12D)-driven lung cancer treatment.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Brian J. Grindel, Brian J. Engel, Justin N. Ong, Anupallavi Srinivasamani, Xiaowen Liang, Niki M. Zacharias, Robert C. Bast, Michael A. Curran, Terry T. Takahashi, Richard W. Roberts, Steven W. Millward
Summary: This study describes the selection of a low nanomolar PD-L1-binding affibody using mRNA display, which showed significant tumor uptake in vivo.
ACS CHEMICAL BIOLOGY
(2022)
Article
Medicine, Research & Experimental
Sergey Deyev, Anzhelika Vorobyeva, Alexey Schulga, Galina Proshkina, Rezan Guler, John Lofblom, Bogdan Mitran, Javad Garousi, Mohamed Altai, Jos Buijs, Vladimir Chernov, Anna Orlova, Vladimir Tolmachev
MOLECULAR PHARMACEUTICS
(2019)
Article
Materials Science, Biomaterials
Rezan Guler, Naresh Thatikonda, Hawraa Ali Ghani, My Hedhammar, John Lofblom
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2019)
Article
Biochemistry & Molecular Biology
Sara S. Rinne, Tianqi Xu, Charles Dahlsson Leitao, Stefan Stahl, John Lofblom, Anna Orlova, Vladimir Tolmachev, Anzhelika Vorobyeva
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Himanshu Chaudhary, Sebastian W. Meister, Henrik Zetterberg, John Lofblom, Christofer Lendel
ACS CHEMICAL NEUROSCIENCE
(2020)
Article
Biochemistry & Molecular Biology
Sara S. Rinne, Charles Dahlsson Leitao, Zahra Saleh-nihad, Bogdan Mitran, Vladimir Tolmachev, Stefan Stahl, John Loefblom, Anna Orlova
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Sebastian W. Meister, Linnea C. Hjelm, Melanie Dannemeyer, Hanna Tegel, Hanna Lindberg, Stefan Stahl, John Lofblom
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Pharmacology & Pharmacy
Charles Dahlsson Leitao, Sara S. Rinne, Mohamed Altai, Olga Vorontsova, Finn Dunas, Per Jonasson, Vladimir Tolmachev, John Lofblom, Stefan Stahl, Anna Orlova
Article
Pharmacology & Pharmacy
Maryam Oroujeni, Tianqi Xu, Katherine Gagnon, Sara S. Rinne, Jan Weis, Javad Garousi, Ken G. Andersson, John Lofblom, Anna Orlova, Vladimir Tolmachev
Summary: This study demonstrated that Ga-66-labeled DFO-ZEGFR:2377 provides higher tumor-to-blood and tumor-to-liver ratios at 24 hours compared to Ga-68-labeled DFO-ZEGFR:2377 at 3 hours. Additionally, Ga-66-labeled DFO-ZEGFR:2377 showed better imaging contrast than Zr-89-labeled DFO-ZEGFR:2377.
Article
Oncology
Sara S. Rinne, Charles Dahlsson Leitao, Ayman Abouzayed, Anzhelika Vorobyeva, Vladimir Tolmachev, Stefan Stahl, John Lofblom, Anna Orlova
Summary: The study suggests that affibody-based tracers are more suitable for PET imaging of HER3 expression, providing better imaging contrast and faster clearance from blood and normal organs.
Article
Biochemistry & Molecular Biology
Sara S. Rinne, Wen Yin, Anna Mestre Borras, Ayman Abouzayed, Charles Dahlsson Leitao, Anzhelika Vorobyeva, John Lofblom, Stefan Stahl, Anna Orlova, Torbjorn Graslund
Summary: This study found that Z(HER3)-ABD-mcDM1 is a highly potent and selective drug conjugate with the ability to specifically target HER3-overexpressing cells.
Article
Biochemical Research Methods
Anna Mestre Borras, Charles Dahlsson Leitao, Stefan Stahl, John Lofblom
Summary: Conditional activation of engineered affinity proteins can be achieved by proteolytic processing. In this study, an anti-idiotypic masking domain was generated to block EGFR-binding on cancer cells when fused to an affibody molecule via a protease cleavage site linker. The results demonstrate the potential therapeutic and diagnostic applications of this approach and suggest further studies are warranted.
Article
Biochemistry & Molecular Biology
Linnea Charlotta Hjelm, My Hedhammar, John Lofblom
Summary: The development of an assay based on brain endothelial cells cultured on permeable recombinant silk nanomembranes for screening the transcytosis capability of biomolecules is described. Evaluation of the assay using an established BBB shuttle antibody showed significant transcytosis over the membranes.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Sebastian W. W. Meister, Luke Parks, Leonie Kolmar, Anna Mestre Borras, Stefan Stahl, John Lofblom
Summary: A combinatorial protease engineering-based screening method was used to redesign the substrate specificity of tobacco etch virus (TEV) protease. This led to the enrichment of a set of protease variants that recognize and cleave a novel target substrate. The method links proteolytic activity to the solubility and correct folding of a fluorescent reporter protein.
BIOTECHNOLOGY JOURNAL
(2023)
Article
Chemistry, Medicinal
Linnea Charlotta Hjelm, Hanna Lindberg, Stefan Stahl, John Lofblom
Summary: The development of biologics for the central nervous system has faced challenges in drug delivery to the brain. Receptor-mediated transcytosis over the blood-brain barrier, particularly targeting the TfR, has been the most successful strategy. Affibody molecules selected for TfR showed promising binding to human TfR, cross-reactivity to the murine orthologue, and binding to TfR-expressing brain endothelial cell lines. Mutagenesis of affibody molecules led to the development of second-generation variants with improved properties, which demonstrated transcytosis ability in an in vitro assay. These TfR-specific affibody molecules have potential as brain shuttles and warrant further investigations.
Article
Biochemistry & Molecular Biology
Linnea Charlotta Hjelm, Hanna Lindberg, Stefan Stahl, John Lofblom
Summary: Affibody molecules are small affinity proteins with excellent properties. A new type of protein scaffold based on a dimeric form of affibodies has been developed, which has a distinct secondary structure content and mode of binding. The scaffold forms a tunnel-like cavity upon binding, encapsulating the target peptide. Selections from a high-complexity phage-displayed library using this scaffold resulted in the identification of high-affinity binders that effectively inhibit amyloid aggregation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)