Review
Chemistry, Medicinal
Aizhan Abdildinova, Mark J. Kurth, Young-Dae Gong
Summary: Peptidomimetics are a unique class of drug molecules, and solid-phase synthesis is an important tool for synthesizing these molecules, where small molecules including heterocycles play a key role as drug cores.
Article
Chemistry, Multidisciplinary
Nassirine Soumanou, Dorthe Lybye, Thomas Hjelmgaard, Sophie Faure
Summary: Highly efficient procedures have been developed for the greener synthesis of sequence-defined peptoid oligomers. The chain elongation process is optimised to be carried out in water-based media, in a unique N to C direction, with a convenient one-pot two-step deprotection/coupling sequence for each new peptoid residue. The process is so efficient that only aqueous extraction is required after each intermediate coupling step, and solvents other than water used during synthesis and workup processes are limited to EtOH, MeOH, or EtOAc.
Article
Chemistry, Multidisciplinary
Abigail Mae Clapperton, Katya Naomi Mariin Vera, Jon Babi, Helen Tran
Summary: This study demonstrates the successful replacement of hazardous and restricted solvents, DMF and NMP, with green and sustainable solvents for the synthesis of polypeptoids.
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(2023)
Review
Chemistry, Organic
Aizhan Abdildinova, Mark J. Kurth, Young-Dae Gong
Summary: Peptidomimetics are compounds with promising pharmacological properties that overcome limitations of peptides through backbone modifications. Accessible synthetic methodologies play a key role in peptidomimetic progress, with solid-phase organic synthesis serving as a powerful tool for their preparation. Numerous strategies for peptide backbone modifications via solid-phase synthesis have been developed in the last two decades.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Lei Huang, Xiao-Ou Zhang, Esteban J. Rozen, Xiaomei Sun, Benjamin Sallis, Odette Verdejo-Torres, Kim Wigglesworth, Daniel Moon, Tingting Huang, John P. Cavaretta, Gang Wang, Lei Zhang, Jason M. Shohet, Mary M. Lee, Qiong Wu
Summary: The protein arginine methyltransferase 5 (PRMT5) regulates the expression of metastasis-related genes by methylating Akt protein, which is required for its phosphorylation and activation, leading to the upregulation of pro-metastatic transcription factors. Moreover, inhibiting PRMT5 can attenuate primary tumor growth and block metastasis in multiple organs, suggesting it may be a potential therapeutic target for high-risk metastatic cancers.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Jinrong Ma, Bin Cai, Shuai Zhang, Tengyue Jian, James J. De Yoreo, Chun-Long Chen, Francois Baneyx
Summary: This study reports a simple and modular approach to hierarchical hybrid synthesis by synthesizing peptoid nanosheets and solid-binding protein to construct stacked multilayered materials, which is expected to be applied in bioimaging and photocatalysis fields.
Article
Chemistry, Multidisciplinary
Animesh Roy, Eric Koesema, Thomas Kodadek
Summary: A powerful quality control method has been developed to distinguish efficiently cyclizing scaffolds during solid-phase synthesis of thioether macrocycles without the need for tedious liquid chromatography/mass spectrometry analysis. This method can also identify linear impurities in a DNA-encoded library of macrocycles and establish a useful quality control protocol for re-synthesis of putative macrocyclic screening hits.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Radhe Shyam, Christiane Forestier, Nicolas Charbonnel, Olivier Roy, Claude Taillefumier, Sophie Faure
Summary: The study combined submonomer synthesis in solution and block-coupling protocols to prepare amphiphilic peptoid hexamers. The amphipathic character was attributed to the hydrophobic aliphatic tert-butyl side-chains and periodically introduced cationic side-chains. Evaluation of the compound's effects on bacterial strains, biofilm formation, and toxicity highlighted the potential of a short constrained peptoid carrying triazolium-type cationic pendant groups.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Hongxiang Wu, Zhenquan Sun, Xuechen Li
Summary: In this study, we introduced N,O-benzylidene acetal dipeptides (NBDs) as robust and effective building blocks for the direct synthesis of difficult peptides and proteins. The versatility of NBDs was demonstrated in the successful synthesis of various challenging peptides and proteins, including chemokine, therapeutic hormones, histone, and glycosylated erythropoietin.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Jan Pawlas, Jon H. Rasmussen
Summary: This study demonstrates the feasibility of using Fmoc/t-Bu solid-phase peptide synthesis under aqueous conditions, utilizing a resin and solvent combination to improve resin swelling and solubility of starting materials. By developing a waste recycling method, the reuse of waste was achieved, reducing the amount of starting materials used and replacing hazardous solvents with an aqueous medium.
Review
Chemistry, Applied
Hong Yan, Fen-Er Chen
Summary: This review highlights the recent progress in solid-phase total synthesis of naturally occurring small peptides from 2014 to July 2021, which not only aids in the identification of peptide structures and synthesis of analogues, but also simplifies the isolation of intermediates.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Biochemistry & Molecular Biology
Xuefei Li, Ningchao Wang, Yuhang Liu, Weipiao Li, Xinyu Bai, Ping Liu, Chun -Yang He
Summary: Peptide-based drugs have gained significant attention in the treatment of various diseases, but their limited pharmacokinetic properties have hindered their full potential. N-methylation is a prominent strategy for enhancing the druggability of peptides, improving their stability, bioavailability, receptor binding affinity, and selectivity. This review provides a comprehensive overview of synthetic methods for N-methylated peptide synthesis and explores the versatile effects of N-methylation on various aspects of peptide properties. The efforts dedicated to N-methylated peptide pharmaceuticals that have obtained marketing approval are also emphasized.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Poriah Strauss, Francesca Nuti, Michael Quagliata, Anna Maria Papini, Mattan Hurevich
Summary: Peptide fragments of glycoproteins with multiple N-glycosylated sites are important tools for studying protein-protein interactions and developing glycopeptide-based diagnostics and immunotherapy. However, the solid-phase synthesis of glycopeptides with multiple N-glycosylated sites is challenging due to difficult couplings and low yield. In this study, we propose an accelerated synthesis approach, called High-Temperature Fast Stirring Peptide Synthesis (HTFS-PS), using heating, stirring, and low-loading solid supports to obtain glycopeptides with multiple N-glycosylated sites.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Organic
Zhen-Sheng Jia, Yong-Jie Wu, Qi-Jun Yao, Xue-Tao Xu, Kun Zhang, Bing-Feng Shi
Summary: A Pd-catalyzed atroposelective C-H allylation with 1,1-disubstituted alkenes was carried out using the chiral ligand L-pGlu-OH, resulting in the synthesis of enantioenriched N-aryl peptoid atropisomers. High yields and excellent enantioselectivities were achieved, with up to 90% yield and 97% ee.
Article
Chemistry, Multidisciplinary
Naveen Gupta, Marcin Wilczek, Lukasz Dobrzycki, Karolina Pulka-Ziach
Summary: The study shows that N-methylation does not alter the structural properties of oligourea foldamers but increases flexibility in the backbone, making it a potentially useful modification for modulating the strength of hydrogen bonds and intermolecular interactions.
Article
Biochemistry & Molecular Biology
Chowdhury Raihan Bikash, Yftah Tal-Gan
ACS CHEMICAL BIOLOGY
(2020)
Article
Chemistry, Medicinal
Ryan W. Mull, Alec A. Brennan, Brittany R. Russ, Yftah Tal-Gan
ACS INFECTIOUS DISEASES
(2020)
Article
Microbiology
Anthony Harrington, Alexis Proutiere, Ryan W. Mull, Laurence du Merle, Shaynoor Dramsi, Yftah Tal-Gan
Summary: Streptococcus gallolyticus subsp. gallolyticus is an emerging opportunistic pathogen responsible for septicemia and endocarditis in the elderly, with invasive infections strongly linked to colorectal cancer (CRC). This pathogen utilizes quorum sensing to regulate bacteriocin production and gain a selective advantage in colonizing the colon. The study conducted the first structure-activity relationship analysis of the quorum sensing pheromone in S. gallolyticus subsp. gallolyticus, revealing unique interactions between streptococcal QS signals.
Article
Biochemistry & Molecular Biology
Tahmina A. Milly, Emilee R. Engler, Kylie S. Chichura, Alec R. Buttner, Bimal Koirala, Yftah Tal-Gan, Michael A. Bertucci
Summary: The study focuses on optimizing the interaction of CSP1 with its transmembrane histidine kinase receptor to weaken pneumococcal infectivity and resistance development. The findings led to the development of potent QS modulators for antimicrobial agents against pneumococcal infections.
Review
Biochemistry & Molecular Biology
Muralikrishna Lella, Yftah Tal-Gan
Summary: Streptococcus pneumoniae is an opportunistic respiratory human pathogen that poses a continuing threat to human health. Recent research has focused on developing alternative methods to attenuate the pathogenicity of S. pneumoniae by targeting the various stages of the non-essential competence regulon communication system, such as introducing promising dominant-negative Competence Stimulating Peptide (CSP) scaffolds. Disrupting CSP export through disturbing the proton motive force, activating the counter signaling circuit, and targeting the pneumococcal proteome are among the strategies discussed to control pneumococcal pathogenicity.
Article
Biochemistry & Molecular Biology
Ryan W. Mull, Yftah Tal-Gan
Summary: The study identified the CSP of S. oligofermentans and investigated its regulatory role in competence, biofilm formation, and hydrogen peroxide production. By systematically replacing amino acid residues and developing a luciferase-based reporter system, the importance of CSP/ComD binding was determined, leading to further exploration of S. oligofermentans as a biotherapeutic against S. mutans infection, with findings of minimal cytotoxicity induction.
ACS CHEMICAL BIOLOGY
(2021)
Article
Biophysics
Korey M. Reid, Abhishek K. Singh, Chowdhury R. Bikash, Jessica Wei, Yftah Tal-Gan, Nguyen Q. Vinh, David M. Leitner
Summary: Proteins and water exhibit dynamic coupling at different time scales. The coupling dynamics between intrinsically disordered proteins (IDPs) and water are found to be more complex compared to structured proteins, potentially due to the interactions between water molecules and charged groups.
BIOPHYSICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Tahmina A. Milly, Alec R. Buttner, Naomi Rieth, Elizabeth Hutnick, Emilee R. Engler, Alexandra R. Campanella, Muralikrishna Lella, Michael A. Bertucci, Yftah Tal-Gan
Summary: Our study demonstrates that introducing bulkier, nonproteogenic side-chain residues can optimize the effects of pneumococcal QS modulators. These substitutions improve the peptide-protein binding interactions, resulting in several potent QS modulators.
RSC CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Medicinal
Muralikrishna Lella, Myung Whan Oh, Shanny Hsuan Kuo, Gee W. Lau, Yftah Tal-Gan
Summary: A library of competitive inhibitors against Streptococcus pneumoniae was constructed and evaluated for their inhibitory effects on the competence regulon. The results demonstrated that these inhibitors can inhibit one group of pneumococcus while activating another group.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Alec A. Brennan, Mona Mehrani, Yftah Tal-Gan
Summary: Understanding bacterial communication mechanisms is crucial for improving our understanding of bacterial infectivity and finding alternative antibacterial therapeutics. This review focuses on the communication mechanisms of Gram-positive bacteria, particularly streptococci, which have demonstrated resistance to traditional antibiotics. Manipulating streptococcal communication circuits and mechanisms is a promising anti-virulence therapeutic approach.
Article
Biochemistry & Molecular Biology
Dominic N. McBrayer, Uttam Ghosh, Muralikrishna Lella, Crissey D. Cameron, Yftah Tal-Gan
Summary: This study systematically investigated the cell-density communication mechanism of Enterococcus faecalis using GBAP and successfully synthesized a series of peptoid-peptide hybrid analogs. The research found that the F7 site in the macrocycle region was tolerant to peptoid modification, while peptoid modification at the N2 site in the exocyclic tail completely abolished activity.
Review
Biochemistry & Molecular Biology
Tahmina A. Milly, Yftah Tal-Gan
Summary: Bacteria use quorum sensing (QS) as a cell density-dependent communication system to coordinate group behaviors. Recent advances in the development of peptide-based modulators have provided new insights into the molecular mechanisms of QS and opened up possibilities for selective inhibition of pathogenic behaviors. Understanding microbial interactions through studying QS could lead to the development of alternative therapeutic agents for bacterial infections.
Article
Microbiology
Alexis Proutiere, Laurence du Merle, Marta Garcia-Lopez, Corentin Leger, Alexis Voegele, Alexandre Chenal, Antony Harrington, Yftah Tal-Gan, Thomas Cokelaer, Patrick Trieu-Cuot, Shaynoor Dramsi
Summary: This study reveals that Streptococcus gallolyticus subsp. gallolyticus (SGG) enhances its colonization of the murine colon under tumoral conditions by producing gallocin A, a two-peptide bacteriocin. The study also characterizes the mechanisms of action and resistance of gallocin A, and emphasizes the importance of the interaction between GllA1 and GllA2 peptides.
MICROBIOLOGY SPECTRUM
(2023)
Article
Chemistry, Medicinal
Myung Whan Oh, Muralikrishna Lella, Shanny Hsuan Kuo, Yftah Tal-Gan, Gee W. Lau
Summary: This study compares the bio-stability, in vitro cytotoxicity, and in vivo toxicity of wild-type CSPs and dominant-negative peptide analogs (dnCSPs), and identifies a peptide analog, CSP1-E1A-cyc(Dap6E10), as a promising therapeutic agent against pneumococcal infection with superior safety and pharmacokinetics profiles.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2022)
Review
Chemistry, Organic
Dominic N. McBrayer, Crissey D. Cameron, Yftah Tal-Gan
ORGANIC & BIOMOLECULAR CHEMISTRY
(2020)