@article{MTMT:2984581, title = {Programmable nanoscaffolds that control ligand display to a G-protein-coupled receptor in membranes to allow dissection of multivalent effects}, url = {https://m2.mtmt.hu/api/publication/2984581}, author = {Dix, AV and Moss, SM and Phan, K and Hoppe, T and Paoletta, S and Kozma, Eszter and Gao, Z-G and Durell, SR and Jacobson, KA and Appella, DH}, doi = {10.1021/ja504288s}, journal-iso = {J AM CHEM SOC}, journal = {JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, volume = {136}, unique-id = {2984581}, issn = {0002-7863}, year = {2014}, eissn = {1520-5126}, pages = {12296-12303} } @article{MTMT:2459240, title = {Foldameric α/β-Peptide Analogs of the β-Sheet-Forming Antiangiogenic Anginex: Structure and Bioactivity}, url = {https://m2.mtmt.hu/api/publication/2459240}, author = {Hegedüs, Zsófia and Wéber, Edit and Kriston-Pál, Éva and Makra, Ildikó and Czibula, Ágnes and Monostori, Éva and Martinek, Tamás}, doi = {10.1021/ja408054f}, journal-iso = {J AM CHEM SOC}, journal = {JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, volume = {135}, unique-id = {2459240}, issn = {0002-7863}, abstract = {The principles of beta-sheet folding and design for alpha-peptidic sequences are well established, while those for sheet mimetics containing homologated amino acid building blocks are still under investigation. To reveal the structure-function relations of beta-amino-acid-containing foldamers, we followed a top-down approach to study a series of alpha/beta-peptidic analogs of anginex, a beta-sheet-forming antiangiogenic peptide. Eight anginex analogs were developed by systematic alpha --> beta(3) substitutions and analyzed by using NMR and CD spectroscopy. The foldamers retained the beta-sheet tendency, though with a decreased folding propensity. beta-Sheet formation could be induced by a micellar environment, similarly to that of the parent peptide. The destructuring effect was higher when the alpha --> beta(3) exchange was located in the beta-sheet core. Analysis of the beta-sheet stability versus substitution pattern and the local conformational bias of the bulky beta(3)V and beta(3)I residues revealed that a mismatch between the H-bonding preferences of the alpha- and beta-residues played a minor role in the structure-breaking effect. Temperature-dependent CD and NMR measurements showed that the hydrophobic stabilization was scaled-down for the alpha/beta-peptides. Analysis of the biological activity of the foldamer peptides showed that four anginex derivatives dose-dependently inhibited the proliferation of a mouse endothelial cell line. The alpha --> beta(3) substitution strategy applied in this work can be a useful approach to the construction of bioactive beta-sheet mimetics with a reduced aggregation tendency and improved pharmacokinetic properties.}, year = {2013}, eissn = {1520-5126}, pages = {16578-16584}, orcid-numbers = {Hegedüs, Zsófia/0000-0002-5546-8167; Wéber, Edit/0000-0002-5904-0619; Czibula, Ágnes/0000-0003-4461-2773; Monostori, Éva/0000-0002-7442-3562; Martinek, Tamás/0000-0003-3168-8066} } @article{MTMT:2034805, title = {A Foldamer-Dendrimer Conjugate Neutralizes Synaptotoxic Beta-Amyloid Oligomers}, url = {https://m2.mtmt.hu/api/publication/2034805}, author = {Fülöp, Lívia and Mándity, István and Juhász, Gábor and Szegedi, Viktor and Hetényi, Anasztázia and Wéber, Edit and Bozsó, Zsolt and Simon, Dóra and Benkő, Mária and Király, Zoltán and Martinek, Tamás}, doi = {10.1371/journal.pone.0039485}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {7}, unique-id = {2034805}, issn = {1932-6203}, abstract = {Background and Aims

Unnatural self-organizing biomimetic polymers (foldamers) emerged as promising materials for biomolecule recognition and inhibition. Our goal was to construct multivalent foldamer-dendrimer conjugates which wrap the synaptotoxic β-amyloid (Aβ) oligomers with high affinity through their helical foldamer tentacles. Oligomeric Aβ species play pivotal role in Alzheimer's disease, therefore recognition and direct inhibition of this undruggable target is a great current challenge.

Methods and Results

Short helical β-peptide foldamers with designed secondary structures and side chain chemistry patterns were applied as potential recognition segments and their binding to the target was tested with NMR methods (saturation transfer difference and transferred-nuclear Overhauser effect). Helices exhibiting binding in the µM region were coupled to a tetravalent G0-PAMAM dendrimer. In vitro biophysical (isothermal titration calorimetry, dynamic light scattering, transmission electron microscopy and size-exclusion chromatography) and biochemical tests (ELISA and dot blot) indicated the tight binding between the foldamer conjugates and the Aβ oligomers. Moreover, a selective low nM interaction with the low molecular weight fraction of the Aβ oligomers was found. Ex vivo electrophysiological experiments revealed that the new material rescues the long-term potentiation from the toxic Aβ oligomers in mouse hippocampal slices at submicromolar concentration.

Conclusions

The combination of the foldamer methodology, the fragment-based approach and the multivalent design offers a pathway to unnatural protein mimetics that are capable of specific molecular recognition, and has already resulted in an inhibitor for an extremely difficult target.

}, keywords = {Neurotoxicity; hippocampus; ARTICLE; MOUSE; controlled study; nonhuman; animal tissue; Protein Binding; in vitro study; POLYMER; unclassified drug; binding affinity; chemical structure; Biophysics; BIOCHEMISTRY; ex vivo study; Oligomer; Nuclear magnetic resonance spectroscopy; protein interaction; amyloid beta protein; chemical binding; long term potentiation; dendrimer; foldamer}, year = {2012}, eissn = {1932-6203}, orcid-numbers = {Fülöp, Lívia/0000-0002-8010-0129; Mándity, István/0000-0003-2865-6143; Szegedi, Viktor/0000-0003-4191-379X; Hetényi, Anasztázia/0000-0001-8080-6992; Wéber, Edit/0000-0002-5904-0619; Bozsó, Zsolt/0000-0002-5713-3096; Martinek, Tamás/0000-0003-3168-8066} } @article{MTMT:1842290, title = {Peptidic foldamers: ramping up diversity}, url = {https://m2.mtmt.hu/api/publication/1842290}, author = {Martinek, Tamás and Fülöp, Ferenc}, doi = {10.1039/c1cs15097a}, journal-iso = {CHEM SOC REV}, journal = {CHEMICAL SOCIETY REVIEWS}, volume = {41}, unique-id = {1842290}, issn = {0306-0012}, abstract = {Non-natural folded polymers (foldamers) display considerable versatility, and the design of such molecules is of great current interest. In this respect, peptidic foldamers are perhaps the best-characterized systems, as they populate a number of residue-controlled secondary structures, which have found various biological applications and have also led to the creation of nanostructured materials. This critical review covers recent developments related to diverse building blocks and modern foldamer design principles, such as the stereochemical patterning methods. The recent achievements concerning tertiary/quaternary structures and the self-assembling foldameric nanostructures are also addressed (176 references).}, keywords = {DE-NOVO DESIGN; BETA-AMINO ACIDS; PROTEINOGENIC SIDE-CHAINS; MODEL SYNTHETIC FOLDAMERS; GCN4 LEUCINE-ZIPPER; HYDROGEN-BONDED RINGS; PARALLEL SHEET STRUCTURE; MIXED ALPHA/BETA-PEPTIDES; HELICAL SECONDARY STRUCTURES; EFFECTIVE SIMULATION PROTOCOLS}, year = {2012}, eissn = {1460-4744}, pages = {687-702}, orcid-numbers = {Martinek, Tamás/0000-0003-3168-8066; Fülöp, Ferenc/0000-0003-1066-5287} } @article{MTMT:2316260, title = {Heparin characterization:challenges and solutions}, url = {https://m2.mtmt.hu/api/publication/2316260}, author = {Jones, C J and Béni, Szabolcs and Limtiaco, J F K and Langeslay, D J and Larive, C K}, doi = {10.1146/annurev-anchem-061010-113911}, journal-iso = {ANNU REV ANAL CHEM}, journal = {ANNUAL REVIEW OF ANALYTICAL CHEMISTRY}, volume = {4}, unique-id = {2316260}, issn = {1936-1327}, year = {2011}, eissn = {1936-1335}, pages = {439-465}, orcid-numbers = {Béni, Szabolcs/0000-0001-7056-6825} }