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We are developing new types of peptide nucleic acids (PNAs) for use in detection of nucleic acids as well as for multivalent display at the nanometer scale. The traditional form of PNA consists of an aminoethylglycine backbone to which nucleobases are attached. These molecules bind to complementary DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) with high affinity and sequence specificity. We have developed chemical strategies that can be used to functionalize and/or pre-organize this class of molecules while preserving the binding properties to complementary nucleic acids. Specifically, we have incorporated a cyclopentane ring into the PNA backbone to enhance the nucleic acid binding properties of PNA. Using this modification, we have shown that detection of nucleic acids derived from pathogens is greatly improved. We are engaged in developing new diagnostic techniques based on this chemically-modified version of PNA. In addition to cyclopentane modifications, we have introduced γ-lysine-modified PNA and developed a method to use this PNA in a novel approach to examine multivalent binding. Multivalent effects dictate the binding affinity of multiple ligands on one molecular entity to receptors. By attaching ligands to the γ-lysine sidechains of the modified PNA, we can assemble libraries of multivalent assemblies and probe for biological activity. Using ligands specific for an integrin receptor, we have shown that the optimized γ-Lys-PNA multivalent scaffold improves biological activity of the ligand by two orders of magnitude in both cell-based and in vivo models of cancer metastasis. Our method should be generally applicable to study any multivalent binding event in biology.
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论文共 189 篇作者统计合作学者相似作者
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ACS Sensorsno. 3 (2024): 1458-1464
Sheethal Thomas Mannully, Rawan Mahajna, Huda Nazzal, Salam Maree,Hongchao Zheng,Daniel H. Appella,Reuven Reich,Eylon Yavin
Biomoleculesno. 6 (2024): 609-609
Jay Prakash Kumar,Dalibor Kosek, Stewart R. Durell,Lisa M. Miller Jenkins,Subrata Debnath,Nathan P. Coussens, Matthew D. Hall,Daniel H. Appella,Fred Dyda, Sharlyn J. Mazur,Ettore Appella
The Journal of biological chemistryno. 8 (2024): 107561-107561
Mohammad Arif Rahman,Massimiliano Bissa,Isabela Silva de Castro,Sabrina Helmold Hait,James D. Stamos,Farzana Bhuyan,Ruth Hunegnaw,Sarkis Sarkis,Anna Gutowska,Melvin N. Doster,Ramona Moles,Tanya Hoang,Lisa M. Miller Jenkins,Ettore Appella,David J. Venzon,Hyoyoung Choo-Wosoba, Timothy Cardozo, Marc M. Baum,Daniel H. Appella,Marjorie Robert-Guroff,Genoveffa Franchini
NATURE MICROBIOLOGYno. 8 (2023): 1600-1600
CHEMICAL COMMUNICATIONSno. 77 (2023): 11593-11593
Mohammad Arif Rahman,Massimiliano Bissa,Isabela Silva de Castro,Sabrina Helmold Hait,James D. Stamos,Farzana Bhuyan,Ruth Hunegnaw,Sarkis,Anna Gutowska,Melvin N. Doster,Ramona Moles,Tanya Hoang,Lisa M. Miller Jenkins,Ettore Appella,David J. Venzon,Hyoyoung Choo-Wosoba,Timothy Cardozo,Marc M. Baum,Daniel H. Appella,Marjorie Robert-Guroff,Genoveffa Franchini
Nature Microbiology (2023): 905-918
ACS pharmacology & translational science (2023)
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#Papers: 189
#Citation: 6337
H-Index: 34
G-Index: 79
Sociability: 6
Diversity: 0
Activity: 1
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