Review
Pharmacology & Pharmacy
Andreea Gostaviceanu, Simona Gavrilas, Lucian Copolovici, Dana Maria Copolovici
Summary: Membrane-active peptides (MAPs) have unique properties that make them valuable tools for studying membrane structure and function and promising candidates for therapeutic applications. They can selectively interact with multiple membranes and disrupt lipid bilayers through different pathways. MAPs have shown antimicrobial activity, selective targeting of cancer cells, and drug delivery capabilities, making them a fascinating class of biomolecules with significant potential in basic research and clinical applications.
Article
Biochemistry & Molecular Biology
Igor S. D. Costa, Tiago Junot, Fernanda L. Silva, Wanessa Felix, Jose L. Cardozo Fh, Antonio F. Pereira de Araujo, Constanca Pais do Amaral, Sonia Goncalves, Nuno C. Santos, Jose R. S. A. Leite, Carlos Bloch Jr, Guilherme D. Brand
Summary: The existence of antimicrobial encrypted fragments in human proteins has been demonstrated, and algorithms have been developed to identify these segments on a large scale. These fragments are typically cationic and amphiphilic segments that exert antimicrobial activity by disrupting membranes. The study found that about 2% of all human proteins contain these segments, with a higher prevalence in transmembrane and peripheral membrane proteins. These segments have conservation scores similar to other residues with similar solvent accessibility.
Article
Biophysics
Emanuelle D. Freitas, Rogerio A. Rataglioli, Josephine Oshodi, Marisa M. Beppu
Summary: The coronavirus pandemic has highlighted the importance of bioactive materials in mitigating viral infections. Bioinspired antimicrobial peptides (AMPs) have emerged as suitable building blocks for antimicrobial coatings due to their versatile design and environmentally friendly features. This review discusses the advances and opportunities in using AMPs to create virucidal coatings, including the fundamental characteristics of peptide structure, advances in coating medical devices, and the role of different materials in designing antiviral coatings.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2022)
Article
Chemistry, Medicinal
Manuel K. Langer, Ataur Rahman, Hymonti Dey, Trude Anderssen, Francesco Zilioli, Tor Haug, Hans -Matti Blencke, Klara Stensvag, Morten B. Strom, Annette Bayer
Summary: This study reports a promising class of antimicrobial agents, amphipathic barbiturate mimics of marine eusynstyelamides. A detailed analysis of the structure-activity relationship for cationic amphipathic barbiturates was conducted, and it was found that different cationic groups, hydrocarbon linkers, and lipophilic side chains had varying effects on their antimicrobial potency and haemolytic activity. Based on these findings, both potent narrow-spectrum and broad-spectrum barbiturates with low or no haemolytic activity were successfully prepared.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Joanna Watly, Adriana Miller, Henryk Kozlowski, Magdalena Rowinska-Zyrek
Summary: The involvement of metal ions in interacting with therapeutic peptides can fine-tune the biological properties of antimicrobial peptides. The use of proteolytically stable peptidomimetics, such as D-, beta-, gamma-amino acids, unnatural amino acids, azapeptides, peptoids, cyclopeptides, and dehydropeptides, provides an infinite reservoir of metal binding motifs for metabolically stable, well-designed, biologically active molecules. This approach offers potential solutions to the problematic metabolic stability of therapeutic peptides.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Tsz Tin Yu, Rajesh Kuppusamy, Muhammad Yasir, Md. Musfizur Hassan, Manjulatha Sara, Junming Ho, Mark D. P. Willcox, David StC. Black, Naresh Kumar
Summary: Peptidomimetics have emerged as a new class of antibacterial agents to combat drug-resistant bacteria. By incorporating hydrophobic and hydrophilic groups into a glyoxamide core, the synthesized compounds showed effective inhibition against Staphylococcus aureus and Escherichia coli biofilms without toxicity to human cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Yongzhi Chen, Hongxia Li, Jiayong Liu, Rongcui Zhong, Haizhou Li, Shanfang Fang, Shouping Liu, Shuimu Lin
Summary: The emergence of bacterial multidrug resistance and the lack of new antimicrobial agents have led to the urgent need for the discovery and development of novel antibacterials. Antimicrobial peptidomimetics have shown promise in overcoming antibiotic resistance and are effective in rapidly killing bacteria without inducing resistance. Specific compounds have demonstrated potent activity against Gram-positive bacteria, low toxicity to mammalian cells, good stability, and high efficacy in treating bacterial infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Mengqi Le, Wen Huang, Zunwei Ma, Zhifeng Shi, Qingtao Li, Caihong Lin, Lin Wang, Yong-Guang Jia
Summary: Cationic dendrimers derived from facially amphiphilic skeletons show high antibacterial activity and biocompatibility, and are more effective and safer than penicillin G in treating infections and promoting wound healing.
Review
Pharmacology & Pharmacy
Amr A. A. Abd El-Aal, Fairen A. Jayakumar, Kavita Reginald
Summary: Cryptides are bioactive peptides embedded in their parent proteins, which have multiple biological functions. Cationic cryptides, with their mechanism less likely to be affected by genetic mutations, could serve as modern drugs in infectious diseases and cancers. This review provides an overview of current understanding of cryptides, sustainable mining methods, and their potential applications in antimicrobial and anticancer therapy.
DRUG DISCOVERY TODAY
(2023)
Article
Multidisciplinary Sciences
Kanchan Tiwari, Madhuri Singh, Prince Kumar, Kasturi Mukhopadhyay
Summary: In this study, the antimicrobial activity of alpha-MSH and its cationic analogues against Escherichia coli was investigated. The results showed that these analogues demonstrated killing of both logarithmic and stationary phase E. coli cells in a time, dose and cationicity-dependent manner. The most cationic analogue, KKK-MSH, successfully eradicated E. coli cells within 15 minutes at a concentration as low as 1 μM. The study suggests that alpha-MSH based cationic peptides hold promise as future agents with broad-spectrum antibacterial efficacy against both Gram-negative and Gram-positive pathogens.
SCIENTIFIC REPORTS
(2022)
Article
Biophysics
Roja Hadianamrei, Mhd Anas Tomeh, Stephen Brown, Jiqian Wang, Xiubo Zhao
Summary: This study focused on the development and characterization of short cationic amphiphilic beta-sheet forming anticancer peptides. The peptides exhibited selective anticancer activity influenced by their surface activity and secondary structure in hydrophobic surfaces, leading to disruption of mitochondrial membranes and apoptosis. Insights gained from the study can be used to design new ACPs with improved anticancer activity and lower toxicity against normal cells.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2022)
Article
Chemistry, Multidisciplinary
Shanfang Fang, Yuan-Ye Dang, Haizhou Li, Hongxia Li, Jiayong Liu, Rongcui Zhong, Yongzhi Chen, Shouping Liu, Shuimu Lin
Summary: Bacteria have become more resistant to current antimicrobial drugs. New antimicrobial drugs are urgently needed to combat drug-resistant pathogens. In this study, we designed and synthesized a series of calix[4]arene derivatives as antibacterial agents, mimicking the structure and functions of antibacterial peptides. After introducing cationic hydrophilic moieties and optimizing the structure, we identified a lead compound (16) with excellent antibacterial activity against Gram-positive bacteria, low toxicity to mammalian cells, and poor hemolytic activity. The mechanism studies showed that compound 16 can directly destroy bacterial cell membranes, leading to bacterial death and low potential for bacterial resistance development.
FRONTIERS IN CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Tatyana V. Vakhrusheva, Grigoriy D. Moroz, Liliya Yu Basyreva, Ekaterina Shmeleva, Sergey A. Gusev, Elena Mikhalchik, Ekaterina N. Grafskaia, Ivan A. Latsis, Oleg M. Panasenko, Vassili N. Lazarev
Summary: This study evaluated the behavior of synthetic short CAMPs in direct contact with blood cells and plasma. The results showed a correlation between CAMP biocompatibility and their effects on blood cell membranes and plasma.
Article
Biophysics
Fang Pan, Yueping Li, Yujie Ding, Songwei Lv, Rongrong You, Roja Hadianamrei, Mhd Anas Tomeh, Xiubo Zhao
Summary: This study systematically designed a series of new alpha-helical short peptides with different anticancer activities and demonstrated their interaction mechanism with cancer cells. The peptides exhibited high selectivity towards cancer cells due to their balanced amphiphilicity and cationic nature, while showing low toxicity to normal cells. Furthermore, the peptides not only damaged the mitochondria and induced apoptosis in cancer cells, but also activated the Caspase enzyme-linked reaction. The results suggest the potential of these peptides for clinical applications and provide guidance for the development of highly selective anticancer medications.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2022)
Article
Biochemistry & Molecular Biology
Katrina Browne, Rajesh Kuppusamy, William R. Walsh, David StC Black, Mark D. P. Willcox, Naresh Kumar, Renxun Chen
Summary: Antibiotic resistance is a global challenge, and combination therapies using antibiotics and antimicrobial peptidomimetics can mitigate the development of resistance in bacteria. This strategy demonstrates synergistic activity against both Gram-positive and Gram-negative bacteria and has significant potential in clinical applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Eike Siebs, Elena Shanina, Sakonwan Kuhaudomlarp, Priscila da Silva Figueiredo Celestino Gomes, Cloe Fortin, Peter H. Seeberger, Didier Rognan, Christoph Rademacher, Anne Imberty, Alexander Titz
Summary: This study reports a new approach to inhibit the formation of Pseudomonas aeruginosa biofilms. By synthesizing galactosidic LecA inhibitors with aromatic moieties targeting the central pocket, the formation of biofilms was successfully reduced.
Article
Microbiology
Marina Borisova, Katja Balbuchta, Andrew Lovering, Alexander Titz, Christoph Mayer
Summary: The periodontal pathogen Tannerella forsythia relies on exo-N-acetylmuramidases to obtain the essential growth factor MurNAc from peptidoglycan sources. Two exo-N-acetylmuramidases, NamZ1 and NamZ2, were found to have different activities in releasing disaccharides and terminal MurNAc monosaccharides, respectively. This study contributes to our understanding of how T. forsythia acquires MurNAc and provides insights for the development of anti-periodontal drugs. It also suggests that the utilization of peptidoglycan as a nutrient source is a common feature among bacteria.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Engineering, Biomedical
Benedikt C. Huck, Durairaj Thiyagarajan, Aghiad Bali, Annette Boese, Karen F. W. Besecke, Constantin Hozsa, Robert K. Gieseler, Marcus Furch, Cristiane Carvalho-Wodarz, Franziska Waldow, Dominik Schwudke, Olga Metelkina, Alexander Titz, Hanno Huwer, Konrad Schwarzkopf, Jessica Hoppstaedter, Alexandra K. Kiemer, Marcus Koch, Brigitta Loretz, Claus-Michael Lehr
Summary: The effect of fucosylated and nonfucosylated liposomes on cellular uptake and delivery was investigated, with fucosylated liposomes showing enhanced bacterial killing effect on nontuberculous mycobacterial infections, suggesting a potential improvement in treatment efficacy.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Miriam Hoffmann, Nicole L. Snyder, Laura Hartmann
Summary: Sulfated glycosaminoglycans (sGAGs) are important in various biological processes and have potential as antiviral compounds. The structure and sulfation patterns of sGAGs play a key role in their biological function. However, synthesizing sGAG mimetics is still challenging. In this study, three groups of sulfated glycomacromolecules were successfully synthesized, demonstrating the wide applicability of this method. The synthesized structures had high purity and sulfation degree, and showed anticoagulant properties similar to natural HS.
Article
Biochemistry & Molecular Biology
Alexander Hoeing, Abbna Kirupakaran, Christine Beuck, Marius Poerschke, Felix C. Niemeyer, Theresa Seiler, Laura Hartmann, Peter Bayer, Thomas Schrader, Shirley K. Knauer
Summary: Many natural proteins utilize flexible loops to interact with their binding partners and undergo structural rearrangements for perfect binding. The molecular recognition of such flexible structures is challenging due to their conformational dynamics. Protein-protein interactions, on the other hand, involve the display of multiple complementary binding partners to enhance affinity and specificity. In this study, advanced multivalent supramolecular tweezers were rationally designed to target specific lysine and arginine clusters on a flexible protein surface loop.
Article
Biochemistry & Molecular Biology
Patrick B. Konietzny, Hannelore Peters, Marc L. Hofer, Ulla I. M. Gerling-Driessen, Robert P. de Vries, Thomas Peters, Laura Hartmann
Summary: Sialoglycans play a key role in biological recognition processes and their multivalent presentation is crucial for high-affinity binding. This study combines solid phase polymer synthesis and enzymatic sialylation to successfully synthesize sequence-defined sialylated macromolecules. Surprisingly, an unexpected side reaction involving Tris-sialoside formation was observed.
MACROMOLECULAR BIOSCIENCE
(2022)
Article
Polymer Science
Miriam Hoffmann, Nicole L. Snyder, Laura Hartmann
Summary: This article provides an overview of the roles of HP/HS in viral engagement and examines historical and recent approaches toward oligo-/polysaccharide, glycopolymer, and anionic polymer HP/HS mimetics. An overview of current applications and future prospects of these molecules is provided, demonstrating their potential in addressing current and future epidemics and pandemics.
Article
Chemistry, Multidisciplinary
Eva Zahorska, Francesca Rosato, Kai Stober, Sakonwan Kuhaudomlarp, Joscha Meiers, Dirk Hauck, Dorina Reith, Emilie Gillon, Katharina Rox, Anne Imberty, Winfried Roemer, Alexander Titz
Summary: The researchers have successfully improved the solubility and stability of divalent galactosides and used them to inhibit the biological activity of Pseudomonas aeruginosa, which is important for the treatment of related infections.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Joscha Meiers, Jan Dastbaz, Sebastian Adam, Sari Rasheed, Susanne H. Kirsch, Peter Meiser, Peter Gross, Rolf Mueller, Alexander Titz
Summary: The highly glycosylated spike protein of SARS-CoV-2 is crucial for infection and is a target for antiviral agents and vaccines. A pineapple-derived lectin AcmJRL has been found to bind mannosides and is present in the medication bromelain. This study showed that AcmJRL binds to the spike protein of SARS-CoV-2 with a low-micromolar K-D in a carbohydrate-dependent manner.
Article
Polymer Science
Alexander Banger, Peter Pasch, Luca-Cesare Blawitzki, Simon Weber, Marius Otten, Cornelia Monzel, Stephan Schmidt, Jens Voskuhl, Laura Hartmann
Summary: This study explores the cell's glycocalyx model by synthesizing amphiphilic glycan-functionalized oligomers and introducing an aggregation-induced luminophore for detection and localization of clustering events in self-assembled structures.
MACROMOLECULAR CHEMISTRY AND PHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Janina Sponsel, Yubing Guo, Lutfir Hamzam, Alice C. Lavanant, Annia Perez-Riveron, Emma Partiot, Quentin Muller, Julien Rottura, Raphael Gaudin, Dirk Hauck, Alexander Titz, Vincent Flacher, Winfried Roemer, Christopher G. Mueller
Summary: Pseudomonas aeruginosa produces a virulence factor, LecB, that binds to endothelial cells and disrupts leukocyte passage, impairing immune response. The lecturer also impacts dendritic cell migration and T cell activation. Inhibiting LecB can restore immune response, highlighting its importance in combating P. aeruginosa infection.
Article
Chemistry, Multidisciplinary
Karolina Wojtczak, Eva Zahorska, Ian J. Murphy, Finnja Koppel, Gordon Cooke, Alexander Titz, Joseph P. Byrne
Summary: Interactions between lectins and glycoconjugate-terbium(iii) self-assembly complexes are utilized for sensing by enhancing lanthanide luminescence. This glycan-directed sensing method can detect an unlabelled lectin (LecA) associated with pathogen P. aeruginosa in solution, without bactericidal activity. Further development of these probes holds potential as a diagnostic tool.
CHEMICAL COMMUNICATIONS
(2023)
Review
Chemistry, Multidisciplinary
Steffen Leusmann, Petra Menova, Elena Shanin, Alexander Titz, Christoph Rademacher
Summary: Carbohydrates play essential regulatory roles in many processes related to health and disease. They are involved in self-/non-self-discrimination, cellular communication, cancer, infection, inflammation, protein folding, function, and life-times. Moreover, carbohydrates are crucial for microbial cell envelopes and biofilm formation. The functions of carbohydrates are mediated by carbohydrate-binding proteins and lectins, and interfering with carbohydrate recognition has become a promising approach for the development of novel therapeutics.
CHEMICAL SOCIETY REVIEWS
(2023)
Article
Chemistry, Medicinal
Patrycja Mala, Eike Siebs, Joscha Meiers, Katharina Rox, Annabelle Varrot, Anne Imberty, Alexander Titz
Summary: This study identified beta-fucosyl amides as high-affinity ligands for LecB, providing a basis for future development into antibacterial drugs.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Joscha Meiers, Katharina Rox, Alexander Titz
Summary: In this study, lectin-targeted antibiotic prodrugs against Pseudomonas aeruginosa were synthesized by conjugating several fluoroquinolones to lectin probes. These prodrugs remained non-toxic in systemic distribution and were activated to exert bactericidal effects only at the infection site. Additionally, the prodrugs exhibited good ADME properties and reduced toxicity.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
