Article
Biochemistry & Molecular Biology
Marshall Case, Tejas Navaratna, Jordan Vinh, Greg Thurber
Summary: Current therapeutics cannot target proteins involved in disease that are inaccessible inside cells and lack small molecule binding pockets. This study uses a technique called SPEED to rapidly screen staple location and linker structure and accelerate peptide design. The results show the importance of this method in studying protein-protein interactions and designing high-affinity peptide antagonists.
ACS CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Lilin Feng, Liang Gao, Daniel F. Sauer, Yu Ji, Haiyang Cui, Ulrich Schwaneberg
Summary: This study presents a facile and reversible method to immobilize a wide range of His(6)-tagged proteins on the E. coli cell surface through Fe(iii)-metal complexes. Successfully, an eGFP and four enzymes with His(6)-tag were immobilized on the cell surface. Moreover, a hydrogel sheath around E. coli cells was generated by immobilizing the His(6)-tagged HRP.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Physical
Naomi Kramer, Ido Sivron, Guillaume Le Saux, Jesus I. Mendieta-Moreno, Nurit Ashkenasy
Summary: The binding of peptides and proteins through multiple weak interactions is widely observed. Biopanning has been used to exploit this multivalent binding for surface functionalization. Understanding the influence of multivalency on binding interactions and surface behavior is crucial for practical applications. In this study, we investigate the relationship between multivalency and the modulation of the surface work function using 12-mer peptides to functionalize indium tin oxide (ITO) surfaces. We demonstrate that the affinity and modulation of the ITO work function by the peptides are linearly dependent on the number of basic residues in the sequence. The multivalent binding interactions result in a peptide crowding effect, leading to a stronger modulation of the work function compared to single amino acid functionalization. This bioderived molecular platform has the potential to eco-friendly enhance optoelectronic device performance.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Microbiology
Benjamin Yu, Julia Kanaan, Hannah Shames, James Wicander, Makunda Aryal, Yunfeng Li, George Korza, Stanley Brul, Gertjan Kramer, Yong-qing Li, Frank C. Nichols, Bing Hao, Peter Setlow
Summary: 2Duf is a protein located in the inner membrane of spores in Bacillus species. The absence of YetF or YdfS leads to decreased resistance to wet heat and damage to spore core components. YetF can modify the inner membrane structure to increase spore resistance to wet heat.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Virology
Marwa Arbi, Imen Larbi, Jihen Nsiri, Imen El Behi, Ahmed Rejeb, Khaled Miled, Adeljelil Ghram, Mehdi Houimel
Summary: This study identified new antiviral peptides that can inhibit the infectivity of H9N2 virus by screening a random linear hexapeptide library. Sixteen different phage-peptides were found to specifically bind to H9N2 virus, and two selected peptides (LSRMPK and FAPRWR) showed antiviral activity in both in ovo and in vivo experiments. These peptides prevent infection by inhibiting the attachment of the H9N2 virus to the cellular receptor.
Article
Chemistry, Multidisciplinary
Ivan Gallego, Javier Ramos-Soriano, Alejandro Mendez-Ardoy, Justo Cabrera-Gonzalez, Irene Lostale-Seijo, Beatriz M. Illescas, Jose J. Reina, Nazario Martin, Javier Montenegro
Summary: Fully substituted peptide/[60]fullerene hexakis-adducts have the potential for multivalent protein recognition and offer synthetically simpler alternatives to natural ligands.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Patrick Weber, Michael Dzuricky, Junseon Min, Irene Jenkins, Ashutosh Chilkoti
Summary: Valency is essential for controlling macromolecular interactions and targeting specific cell types. By using core-crosslinkable micelles, researchers have overcome the issue of critical micelle concentration (CMC)-dependent disassembly, maintaining the targeting ability of nanoparticles in solid tumors.
Article
Biochemical Research Methods
Thomas C. Donahue, Guanghui Zong, Chong Ou, Philip DeShong, Lai -Xi Wang
Summary: In this study, catanionic vesicles were used as a stable lipid-based nanoparticle scaffold for displaying multivalent glycans, which showed enhanced affinity for lectins and could be used for drug delivery and intervention of protein-carbohydrate interactions implicated in disease.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Leslie W. Chan, Kelsey E. Hern, Chayanon Ngambenjawong, Katie Lee, Ester J. Kwon, Deborah T. Hung, Sangeeta N. Bhatia
Summary: Researchers have successfully improved the intracellular delivery of antibiotics to Gram-negative pathogens by engineering macromolecular potentiators WD40, which reduced the minimum inhibitory concentrations of drugs, especially for antibiotics with hydrophobic and highly three-dimensional structures.
ACS INFECTIOUS DISEASES
(2021)
Review
Biotechnology & Applied Microbiology
Peter Setlow, Graham Christie
Summary: Spores can spread food spoilage, diseases, and intoxications, and methods for spore killing include heat, radiation, high pressure, and chemicals. Factors to consider in choosing methods for spore killing include cost, efficacy, operation scope, and compatibility.
WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Tao Wang, Ravikumar Jimmidi, Benoit Roubinet, Ludovic Landemarre, Stephane P. Vincent
Summary: The study investigated the impact of gold nanoparticles of different sizes and ligand densities on multivalent carbohydrate-protein interactions. It was found that gold nanoparticles with a diameter of 20 nm bearing glycofullerenes exhibited the strongest binding ability towards both DC-SIGN and FimH, making them effective anti-adhesive materials for various bacterial and viral pathogens.
Article
Chemistry, Medicinal
Valentin Jakob, Ben G. E. Zoller, Julia Rinkes, Yingwen F. Wu, Alexander Kiefer, Michael Hust, Saskia M. Polten, Andrew J. White, Peta Harvey, Thomas J. Durek, David Craik, Andreas Siebert, Uli Kazmaier, Martin Empting
Summary: Small macrocyclic peptides have potential as new anti-infective drugs, with cyclisation being essential for their activity. Designed disulfide mimetics and a triazole analogue showed activity against different bacterial targets, providing a starting point for medicinal chemistry optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Patrick Gonschorek, Alessandro Zorzi, Tamara Maric, Mathilde Le Jeune, Mischa Schuettel, Mathilde Montagnon, Rebeca Gomez-Ojea, Denis Patrick Vollmar, Chantal Whitfield, Luc Reymond, Vanessa Carle, Hitesh Verma, Oliver Schilling, Alain Hovnanian, Christian Heinis
Summary: In this study, selective and high-affinity inhibitors of KLK5 and KLK7 were identified using phage display. The stability and half-life of the inhibitors were improved by eliminating proteaseprone sites and conjugating them to an albumin-binding peptide. These inhibitors were shown to reach the target KLKs in mouse epidermis and have the potential to control deregulated protease activity in Netherton syndrome.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Rachele Isticato
Summary: Mucosal vaccines have advantages such as inducing adaptive immunity and needle-less vaccinations, but their development is currently limited. Innovative antigens, efficient adjuvants, and delivery systems are crucial for effective mucosal vaccines. Bacterial spores have shown promise as antigen vehicles due to their unique structure and ability to induce protective immune responses when mucosally administered.
Article
Chemistry, Multidisciplinary
Tine Curk, Galina V. Dubacheva, Alain R. Brisson, Ralf P. Richter
Summary: In this study, a theoretical model is derived to investigate the impact of cofactors or competitors on multivalent interactions. It is found that the effect of participating moieties can be accurately captured by rescaling the affinity constant of ligand-receptor bonds. Experimental data support the theoretical predictions and demonstrate the superselectivity of multivalent binding in the presence of cofactors or competitors.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Oncology
Zhuo-Xun Wu, Yuqi Yang, Qiu-Xu Teng, Jing-Quan Wang, Zi-Ning Lei, Jing-Qiu Wang, Sabrina Lusvarghi, Suresh V. Ambudkar, Dong-Hua Yang, Zhe-Sheng Chen
Article
Multidisciplinary Sciences
Diogo Henrique Kita, Nathalie Guragossian, Ingrid Fatima Zattoni, Vivian Rotuno Moure, Fabiane Gomes de Moraes Rego, Sabrina Lusvarghi, Thomas Moulenat, Billel Belhani, Geraldo Picheth, Sofiane Bouacida, Zouhair Bouaziz, Christelle Marminon, Malika Berredjem, Joachim Jose, Marcos Brown Goncalves, Suresh V. Ambudkar, Glaucio Valdameri, Marc Le Borgne
Summary: A new generation of indeno[1,2-b]indole compounds were synthesized and tested as ABCG2 inhibitors, showing potent inhibition activity and ability to fully chemosensitize cancer cells. These compounds exert their effects by stimulating ABCG2 ATPase activity and stabilizing the protein structure.
SCIENTIFIC REPORTS
(2021)
Article
Pharmacology & Pharmacy
Chung-Pu Wu, Tai-Ho Hung, Sabrina Lusvarghi, Yi-Hsuan Chu, Sung-Han Hsiao, Yang-Hui Huang, Yu-Tzu Chang, Suresh V. Ambudkar
Summary: The study found that Almonertinib can inhibit the drug transport activity of ABCBl at submicromolar concentrations, but not affect ABCG2, and resensitize multidrug-resistant cancer cells overexpressing ABCB1 to chemotherapeutic drugs.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Sabrina Lusvarghi, Stewart R. Durell, Suresh V. Ambudkar
Summary: This study demonstrates that the ATP hydrolysis-defective mutant does not follow the same steps as the wild-type P-gp. The conformational differences in the EQ mutant may provide insights into the catalytic cycle of P-gp, suggesting the need for additional structural studies with the wild-type protein.
Article
Biochemistry & Molecular Biology
Chung-Pu Wu, Cheng-Yu Hung, Sabrina Lusvarghi, Yen-Fu Chang, Sung-Han Hsiao, Yang-Hui Huang, Tai-Ho Hung, Jau-Song Yu, Suresh. V. Ambudkar
Summary: The study revealed that the multidrug efflux transporters ABCB1 and ABCG2 play a crucial role in reducing the sensitivity of human cancer cells to citarinostat by decreasing its activity against HDAC6 and intracellular accumulation of the drug. Co-administration of citarinostat with inhibitors of ABCB1 and ABCG2 may optimize its therapeutic application in the clinic.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Yuqi Yang, Zhuo-Xun Wu, Jing-Quan Wang, Qiu-Xu Teng, Zi-Ning Lei, Sabrina Lusvarghi, Suresh V. Ambudkar, Zhe-Sheng Chen, Dong-Hua Yang
Summary: OTS964 is a potent inhibitor of TOPK that interacts with ABCG2 to affect multidrug resistance, and has an upregulating effect on ABCG2 transporter. It enhances resistance to ABCG2 substrate-drugs by inhibiting efflux function mediated by ABCG2.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Srijani Sarkar, Bruce A. Armitage
Summary: This study designed gamma-modified peptide nucleic acid (gamma PNA) oligomers to target a newly identified guanine-rich gene sequence in the WNV genome, showing potential for inhibiting WNV replication and transcription. The gamma PNAs demonstrated strong binding to the target with low femtomolar affinity at physiological temperature, indicating a promising antiviral strategy.
ACS INFECTIOUS DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Johnathan M. Goldman, Soyoung Kim, Sarah Narburgh, Bruce A. Armitage, James W. Schneider
Summary: miRNA is a promising class of biomarkers, but their low abundance and high sequence homology make detection difficult. A new method using gamma PNAA and DNA nanotags in MTE allows for independent detection of seven members of the let-7 miRNA family, with strong tolerance to serum proteins.
Article
Virology
Sabrina Lusvarghi, Wei Wang, Rachel Herrup, Sabari Nath Neerukonda, Russell Vassell, Lisa Bentley, Ann E. Eakin, Karl J. Erlandson, Carol D. Weiss, Kanta Subbarao
Summary: Mutations in the spike protein of SARS-CoV-2 variants can compromise the effectiveness of therapeutic antibodies. To predict antibody potency against emerging variants, researchers evaluated 25 clinical-stage therapeutic antibodies for neutralization activity against 60 pseudoviruses with single or multiple substitutions in spike domains. They found that most combination and polyclonal therapeutic antibodies remained potent, but key substitutions in variants with multiple spike substitutions predicted resistance.
JOURNAL OF VIROLOGY
(2022)
Article
Virology
Sabari Nath Neerukonda, Russell Vassell, Sabrina Lusvarghi, Richard Wang, Fernando Echegaray, Lisa Bentley, Ann E. Eakin, Karl J. Erlandson, Leah C. Katzelnick, Carol D. Weiss, Wei Wang
Summary: The B.1.617 lineage variants, including Kappa (B.1.617.1) and Delta (B.1.617.2, AY), emerged during the second wave of infections in India. Delta variants have become dominant globally and continue to evolve. The study found that B.1.617 variants showed modest reductions in neutralization by convalescent and vaccine-elicited sera, and some therapeutic antibodies lost neutralization effectiveness against these variants.
Article
Multidisciplinary Sciences
Robert W. Robey, Andrea N. Robinson, Fatima Ali-Rahmani, Lyn M. Huff, Sabrina Lusvarghi, Shahrooz Vahedi, Jordan M. Hotz, Andrew C. Warner, Donna Butcher, Jennifer Matta, Elijah F. Edmondson, Tobie D. Lee, Jacob S. Roth, Olivia W. Lee, Min Shen, Kandice Tanner, Matthew D. Hall, Suresh Ambudkar, Michael M. Gottesman
Summary: This research investigated two genes, abcb4 and abcb5, similar to ABCB1 in the zebrafish BBB, unveiling differences in substrate resistance between Abcb4 and Abcb5. Abcb4 demonstrated overlapping substrate specificity with P-gp, suggesting its functional resemblance to P-gp, making zebrafish a potential model for studying P-gp at the BBB.
SCIENTIFIC REPORTS
(2021)
Editorial Material
Biochemistry & Molecular Biology
Bruce A. Armitage
Article
Biochemistry & Molecular Biology
Srijani Sarkar, Gabriela Colon-Roura, Alexander Pearse, Bruce A. Armitage
Summary: This study developed synthetic molecules, PNA and gamma PNA, capable of targeting i-motif DNA structures. The biophysical experiments demonstrated the successful invasion of i-motif by PNA and gamma PNA, showing strong binding and high thermal stability. Targeting KRAS transcription using high-affinity oligonucleotide mimics like gamma PNAs may offer a potential anti-cancer strategy.
Article
Chemistry, Medicinal
Barry J. Liang, Sabrina Lusvarghi, Suresh Ambudkar, Huang-Chiao Huang
Summary: Efforts to overcome cancer multidrug resistance through inhibition of ABC drug transporters have largely failed, prompting a need for new strategies. This study demonstrates how photodynamic therapy can manipulate the function and integrity of ABC drug transporters to overcome resistance, providing insights for the development of new optical tools.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2021)
Article
Nanoscience & Nanotechnology
Barry J. Liang, Sabrina Lusvarghi, Suresh Ambudkar, Huang-Chiao Huang
Summary: Accurate detection of ABCB1 expression is crucial for identifying drug-resistant tumors. A new photoimmunoconjugate combining a clinically approved BPD photosensitizer and a conformational-sensitive UIC2 monoclonal antibody has been developed to target functionally active human ABCB1.
Article
Chemistry, Organic
Faiza Diaba, Gisela Trenchs
Summary: The first violet light-mediated synthesis of gamma- and delta-lactams from N-alkenyl trichloroacetamides is reported in this paper. The reactions are conducted in tetrahydrofuran or 2-methyltetrahydrofuran as the sole solvent without catalysts or additives, under non-anhydrous conditions in an air atmosphere where the solvent serves as the radical initiator.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Feroze Hussain, Sajjad Ahmed, Ashiq Hussain Padder, Qazi Naveed Ahmed
Summary: This study reports a novel and efficient one-pot synthesis method for mixed phosphorotrithioates, which does not require supplementary additives and shows broad applicability.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Hyunjin Oh, Ikyon Kim
Summary: A new 1,2,4-triazole-pyrrolo[1,2-a]pyrazine hybrid system, 6-acylpyrrolo[1,2-a][1,2,4]triazolo[5,1-c]pyrazine, was synthesized using a catalyst-free method. This method involved sequential exposure of pyrrole-2-carbonitrile-derived substrates to DMF-DMA and acyl hydrazide, resulting in the formation of acylated pyrazine and 1,2,4-triazole rings, enabling the installation of various substituents at specific positions on the core skeleton.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Ming Yan, Si-fan Wang, Yong-po Zhang, Jin-zhong Zhao, Zhuo Tang, Guang-xun Li
Summary: Here we developed an efficient photocatalytic approach for the convenient preparation of sulfinamides. The reaction allows for the gram-scale preparation of sulfinamides and the one-pot synthesis of various sulfonyl amides.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Farzaneh Bandehali-Naeini, Zahra Tanbakouchian, Noushin Farajinia-Lehi, Nicolas Mayer, Morteza Shiri, Martin Breugst
Summary: Two tandem catalytic systems were developed for the synthesis of novel 3,4-disubstituted maleimides using the same Ugi adducts. Different maleimide structures can be synthesized using either Pd or Cu catalysis.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Tanya Raghava, Anjan Chattopadhyay, Subhadeep Banerjee, Nivedita Sarkar
Summary: Amine substitution of two ortho fluorine atoms of tetrafluoroterephthalonitrile through SNAr chemistry is easily achievable. But further fluorine substitution is only possible under forcing conditions, yielding valuable fluorophores for bioimaging.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Review
Chemistry, Organic
Anju Chadha, Santosh Kumar Padhi, Selvaraj Stella, Sowmyalakshmi Venkataraman, Thangavelu Saravanan
Summary: Alcohol dehydrogenases are enzymes that use cofactors for oxidation or reduction reactions of alcohols or carbonyl compounds. They are utilized in green chemistry and have applications in the production of pharmaceuticals. Recombinant enzymes have solved the challenge of producing purified enzymes in large quantities. Engineered alcohol dehydrogenases have been used in asymmetric synthesis in industry. Various methods have been established for regenerating expensive cofactors to make the enzymatic process more efficient and economically viable.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)