Article
Chemistry, Organic
Yue Zhang, Ruijuan Yin, Hao Jiang, Chaoming Wang, Xiao Wang, Dongping Wang, Kai Zhang, Rilei Yu, Xuechen Li, Tao Jiang
Summary: In this study, a new method for peptide stapling using bifunctional triazine moieties was developed. This method efficiently stabilizes unprotected peptides by conjugating to the phenolic hydroxyl groups of tyrosine. The application of this method to the RGD peptide, which targets integrins, showed significantly improved plasma stability and integrin-targeting ability.
Article
Chemistry, Multidisciplinary
Richard Morewood, Christoph Nitsche
Summary: Stapling peptides can improve their potential as drug candidates, and the activity can be adjusted by tailored linkers. In the search for inhibitors of the Zika virus protease, the length of the linker in the peptide staple was crucial for maximizing activity.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Organic
Jian Li, Weihong Lai, Ao Pang, Lu Liu, Lianbao Ye, Xiao-Feng Xiong
Summary: Cyclic peptides are highly promising therapeutic agents in drug discovery due to their good affinity and selectivity. In this study, an on-resin synthesis of aryl thioether containing peptides and a concise cyclization strategy via chemoselective cysteine SNAr reaction were developed. The constructed cyclic peptides exhibited increased cellular uptakes compared to their linear counterparts.
Article
Biochemistry & Molecular Biology
Yixuan Wang, Hongyong Wang, Mohd Shahnawaz Khan, Fohad Mabood Husain, Saheem Ahmad, Li Bian
Summary: The glycation reaction is a major cause of diabetes and metabolic disorders, and can be discontinued using inhibitors or drugs. While aminoguanidine (AG) is nephrotoxic, bioconjugation with gold nanoparticles (Gnps) can mitigate its toxic effect and enhance its efficacy on glycation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Polymer Science
B. E. Eichinger
Summary: The power law describing the distribution of molecular weights for polymerizations via step-growth ring expansion differs from that of ring-chain equilibria, affecting the distribution of macrocycle molecular weights significantly.
Article
Biochemistry & Molecular Biology
Anita Toscani, Rossana Denaro, Sergio Fernando Castillo Pacheco, Matteo Biolatti, Silvia Anselmi, Valentina Dell'Oste, Daniele Castagnolo
Summary: A series of amidinourea compounds have been synthesized as potential non-nucleoside anti-HSV agents, showing micromolar activity against HSV-1 with low cytotoxicity. These compounds act in an early stage of the HSV replication cycle, just after viral attachment and entry.
Article
Chemistry, Organic
Myoun-Su Kim, Munhyung Bae, Myoung Chong Song, Sunghoon Hwang, Dong-Chan Oh, Yeo Joon Yoon
Summary: Mohangamide A is a pseudo-dimeric nonribosomal peptide synthesized together with WS9326A, and is expected to be formed by the head-to-tail cyclodimerization of linear WS9326A and another identical peptide chain with a different acyl side chain. In vitro experiments showed that this cyclodimerization reaction is directed by the substrate structures and occurs only with both linear intermediates.
Article
Polymer Science
Rui Hu, Liang Gao, Chunhua Cai, Jiaping Lin, Zuowei Chen, Liquan Wang
Summary: This study reports a supramolecular ring-chain competition reaction between the intermicellar polymerization and intramicellar cyclization of rodlike micelles assembled from rod-coil graft copolymers. Nanowires and toroidal micelles are formed as chain-like and ring-like products, respectively. The competition between the two reactions can be induced and regulated by varying the reaction conditions, with the interplay of core/shell interfacial energy, bending energy of rodlike micelles, and end-capping energy determining the ring-chain competition process.
Article
Chemistry, Multidisciplinary
Saan Voss, Joerg Rademann, Christoph Nitsche
Summary: The study introduces a new strategy to generate bicyclic peptides with superior drug properties under physiological conditions, demonstrating their potential in biochemical screening assays, as well as their inhibitory effects on proteases from Zika and West Nile viruses.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Suze Ma, Wenhui Xi, Shu Wang, Heng Chen, Sijia Guo, Tianlu Mo, Wenxue Chen, Zixin Deng, Fener Chen, Wei Ding, Qi Zhang
Summary: This study discovered and characterized two novel daropeptides that lack the C-C cross-link present in darobactin, and revealed the multifunctionality of daropeptide maturases in catalyzing different chemical reactions depending on the substrate motifs.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Richard Morewood, Christoph Nitsche
Summary: Constrained peptides are promising next-generation therapeutics, and peptide stapling is an effective technique to improve the biological activity and metabolic stability of constrained macrocycles. A biocompatible two-component stapling approach based on 2,6-dicyanopyridine and a pseudo-cysteine amino acid allows for efficient stapling either during solid-phase synthesis or following isolation of linear peptides. The orthogonal stapling reaction in aqueous solution at physiological pH enables its direct use in biochemical assays, and successful identification of constrained peptide inhibitors has been demonstrated through a small screening campaign targeting the Zika virus protease NS2B-NS3.
Article
Chemistry, Organic
Liangliang Song, Zhenwei Lv, Yan Li, Kui Zhang, Erik V. Van der Eycken, Lingchao Cai
Summary: In this study, a Rh(III)-catalyzed C-H activation/annulation reaction was developed for the diversification of Lys-based peptides, yielding a range of peptide-isoquinolone conjugates. This method offers racemization-free conditions, high atom and step economy, excellent chemo- and site-selectivity, and broad substrate scope. Furthermore, the peptide-isoquinolone conjugates demonstrate good fluorescent properties and show potential antifungal activity against crop and forest pathogenic fungi, with a particular conjugate exhibiting superior activity compared to the positive control.
Article
Medicine, Research & Experimental
Tomislav Kostic, Dejan Popovic, Zoran Perisic, Dragana Stanojevic, Sonja Dakic, Sandra Saric, Danijela Djordjevic Radojkovic, Svetlana Apostolovic, Nenad Bozinovic, Snezana Ciric Zdravkovic, Stefan Milutinovic, Bojan Maricic, Nikola Zivkovic, Mladjan Golubovic, Miodrag Djordjevic, Radomir Damjanovic, Abraham Bell, Boris Dindic
Summary: The study demonstrates that aminoguanidine has a significant hepatoprotective effect in acute liver damage induced by CCl4, attributed to its antioxidant effects, inhibition of pro-oxidative and pro-inflammatory mediators, and induction of damaged hepatocytes into apoptosis.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Chemistry, Multidisciplinary
Yuanhao Wang, Madeleine M. Joullie
Summary: This article discusses the synthetic strategies of cyclopeptide alkaloids to overcome the challenge of their low availability in nature.
Article
Multidisciplinary Sciences
Bo Li, Lan Wang, Xiangxiang Chen, Xin Chu, Hong Tang, Jie Zhang, Gang He, Li Li, Gong Chen
Summary: In this study, a method for macrocyclization of two free-amine-containing residues in mild conditions is disclosed. This method can efficiently generate complex peptide structures, expanding the toolbox for peptide chemistry.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Organic
Kate Lauder, Daniele Castagnolo
Article
Chemistry, Medicinal
Meir Touitou, Fabrizio Manetti, Camila Maringolo Ribeiro, Fernando Rogerio Pavan, Nicolo Scalacci, Katarina Zrebna, Neelu Begum, Dorothy Semenya, Antima Gupta, Sanjib Bhakta, Timothy D. McHugh, Hanoch Senderowitz, Melina Kyriazi, Daniele Castagnolo
ACS MEDICINAL CHEMISTRY LETTERS
(2020)
Review
Biochemistry & Molecular Biology
Silvia Anselmi, Nandini Aggarwal, Thomas S. Moody, Daniele Castagnolo
Summary: Sulfoxides, important organic compounds widely used in pharmaceutical and organic chemistry, can be synthesized enantioenriched through various biocatalytic approaches. Recent advances include the use of reductive enzymes and unconventional solvents, such as ionic liquids and deep eutectic solvents, for greener and more sustainable synthetic pathways.
Article
Chemistry, Medicinal
Anita Toscani, Charlotte Hind, Melanie Clifford, Seong-Heun Kim, Antonia Gucic, Charlotte Woolley, Naima Saeed, Khondaker Miraz Rahman, J. Mark Sutton, Daniele Castagnolo
Summary: The study reports the synthesis and biological evaluation of a series of phenanthroline-based visible-light-activated manganese(I) carbon-monoxide-releasing molecules (PhotoCORMs) against ESKAPE bacteria and bacterial biofilms. These PhotoCORMs release CO under blue light irradiation and show effective antibacterial activity against multidrug-resistant bacteria, with potential applications in combating antimicrobial resistance.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Seong-Heun Kim, Dorothy Semenya, Daniele Castagnolo
Summary: Compounds with guanidine moieties have been utilized in designing novel drugs for various diseases due to their hydrogen-bonding capability and protonatability. This review focuses on recent advances in studying antimicrobial guanidine-containing compounds, emphasizing their structural diversity and pharmacological relevance.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Anita Toscani, Rossana Denaro, Sergio Fernando Castillo Pacheco, Matteo Biolatti, Silvia Anselmi, Valentina Dell'Oste, Daniele Castagnolo
Summary: A series of amidinourea compounds have been synthesized as potential non-nucleoside anti-HSV agents, showing micromolar activity against HSV-1 with low cytotoxicity. These compounds act in an early stage of the HSV replication cycle, just after viral attachment and entry.
Article
Chemistry, Medicinal
Dorothy Semenya, Meir Touitou, Camila Maringolo Ribeiro, Fernando Rogerio Pavan, Luca Pisano, Vinayak Singh, Kelly Chibale, Georg Bano, Anita Toscani, Fabrizio Manetti, Beatrice Gianibbi, Daniele Castagnolo
Summary: A series of indolyl-3-methyleneamines were designed and synthesized for investigation as new chemical entities against Mycobacterium tuberculosis (Mtb). Compound 7j displayed potent activity and may inhibit Mtb through a unique mechanism.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Fei Zhao, Kate Lauder, Siyu Liu, James D. Finnigan, Simon B. R. Charnock, Simon J. Charnock, Daniele Castagnolo
Summary: This study describes the development of novel biocatalytic and chemoenzymatic methods for the enantioselective synthesis of chiral beta-hydroxysulfides using ketoreductase enzymes. Four ketoreductases were discovered and isolated, enabling the synthesis of beta-hydroxysulfides with different configurations. By utilizing novel chemoenzymatic and biocatalytic reactions or dynamic kinetic resolution, high enantioselective synthesis was achieved using commercially available starting materials.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Medicinal
Guilherme F. S. Fernandes, Andrew M. Thompson, Daniele Castagnolo, William A. Denny, Jean L. Dos Santos
Summary: Tuberculosis (TB) has taken more lives than any other infectious disease in the past 2000 years. Despite the comparable death toll with COVID-19 in 2020, the World Health Organization emphasizes the need for new TB drugs to end this pandemic. However, only a small fraction of the promising anti-TB compounds reported annually successfully reach clinical development.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Alice Benzi, Lara Bianchi, Gianluca Giorgi, Massimo Maccagno, Giovanni Petrillo, Domenico Spinelli, Cinzia Tavani
Summary: Nitrostilbenes with different aryl substituents can be obtained from the initial ring-opening of 3-nitrobenzo[b]thiophene with amines. These versatile compounds exhibit diverse reactivity and can undergo electrocyclization to form novel naphthodihydrofurans. Aromatization and electrocyclization of these compounds further lead to valuable polycondensed O-heterocycles.
Article
Chemistry, Medicinal
Dorothy Semenya, Meir Touitou, Domiziana Masci, Camila Maringolo Ribeiro, Fernando Rogerio Pavan, Guilherme Felipe Dos Santos Fernandes, Beatrice Gianibbi, Fabrizio Manetti, Daniele Castagnolo
Summary: The exploration around the 2,5-dimethylpyrrole scaffold of antitubercular hit compound 1 has led to the discovery of new derivatives that are active against Mycobacterium tuberculosis and multidrug-resistant clinical isolates. Some of these derivatives showed promising cytotoxicity profiles and were effective in inhibiting the growth of intracellular mycobacteria.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Physical
Silvia Anselmi, Alexandra T. P. Carvalho, Angela Serrano-Sanchez, Jose L. Ortega-Roldan, Jill Caswell, Iman Omar, Gustavo Perez-Ortiz, Sarah M. Barry, Thomas S. Moody, Daniele Castagnolo
Summary: This study identifies selective and robust MsrA biocatalysts capable of efficiently catalyzing enantioselective reduction of various aromatic and aliphatic chiral sulfoxides at concentrations of 8-64 mM with high yields and excellent enantiomeric excess (up to 99%). Through rational mutagenesis design using in silico docking, molecular dynamics, and structural nuclear magnetic resonance (NMR) studies, a mutant enzyme MsrA33 was developed, which can catalyze the kinetic resolution of bulky sulfoxide substrates with non-methyl substituents on the sulfur atom with enantiomeric excess up to 99%, overcoming a significant limitation of current MsrA biocatalysts.
Article
Chemistry, Physical
Haoyue Xiang, Salvatore Ferla, Carmine Varricchio, Andrea Brancale, Nicola L. Brown, Gary W. Black, Nicholas J. Turner, Daniele Castagnolo
Summary: Two enzymatic strategies were developed to oxidize 1,2,3,4-tetrahydroquinolines (THQs) and N-cyclopropyl-N-alkylanilines into quinolines and 2-quinolones, respectively. Whole cells and monoamine oxidase (MAO-N) enzymes were used for the biotransformation of THQs, while horseradish peroxidase (HRP)-catalyzed annulation/aromatization reaction followed by Fe-mediated oxidation was employed for the conversion of N-cyclopropyl-N-alkylanilines into 2-quinolone compounds.
Review
Biochemistry & Molecular Biology
Guilherme Felipe Santos Fernandes, Caue Benito Scarim, Seong-Heun Kim, Jingyue Wu, Daniele Castagnolo
Summary: Oxazolidinone is a five-member heterocyclic ring with diverse applications in medicinal chemistry. Among the isomers, 2-oxazolidinone has been extensively explored and numerous analogues have been developed. Despite promising pharmacological applications in various therapeutic areas, most oxazolidinone derivatives have not progressed beyond the initial stages of drug development. This review highlights the efforts of medicinal chemists in exploring this scaffold and emphasizes its potential for medicinal chemistry.
RSC MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Silvia Anselmi, Siyu Liu, Seong-Heun Kim, Sarah M. Barry, Thomas S. Moody, Daniele Castagnolo
Summary: A mild, chemoselective and sustainable biocatalysed synthesis of sulfoxides has been developed with CALB and AcOEt, leading to high yields and excellent E-factors in the synthesis of a range of sulfoxides, including the drug omeprazole.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)