TY - JOUR AU - Dix, AV AU - Moss, SM AU - Phan, K AU - Hoppe, T AU - Paoletta, S AU - Kozma, Eszter AU - Gao, Z-G AU - Durell, SR AU - Jacobson, KA AU - Appella, DH TI - Programmable nanoscaffolds that control ligand display to a G-protein-coupled receptor in membranes to allow dissection of multivalent effects JF - JOURNAL OF THE AMERICAN CHEMICAL SOCIETY J2 - J AM CHEM SOC VL - 136 PY - 2014 IS - 35 SP - 12296 EP - 12303 PG - 8 SN - 0002-7863 DO - 10.1021/ja504288s UR - https://m2.mtmt.hu/api/publication/2984581 ID - 2984581 N1 - Hiányzó Jelleg: 'JOUR\n\nArticle' Megjegyzés-25231883 Hiányzó Jelleg: 'JOUR\n\nArticle' Admin megjegyzés-25231883 tblcategory: (Category) ('JOUR\n\nArticle') #Jelleg LA - English DB - MTMT ER - TY - JOUR AU - Hegedüs, Zsófia AU - Wéber, Edit AU - Kriston-Pál, Éva AU - Makra, Ildikó AU - Czibula, Ágnes AU - Monostori, Éva AU - Martinek, Tamás TI - Foldameric α/β-Peptide Analogs of the β-Sheet-Forming Antiangiogenic Anginex: Structure and Bioactivity JF - JOURNAL OF THE AMERICAN CHEMICAL SOCIETY J2 - J AM CHEM SOC VL - 135 PY - 2013 IS - 44 SP - 16578 EP - 16584 PG - 7 SN - 0002-7863 DO - 10.1021/ja408054f UR - https://m2.mtmt.hu/api/publication/2459240 ID - 2459240 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Fülöp, Lívia AU - Mándity, István AU - Juhász, Gábor AU - Szegedi, Viktor AU - Hetényi, Anasztázia AU - Wéber, Edit AU - Bozsó, Zsolt AU - Simon, Dóra AU - Benkő, Mária AU - Király, Zoltán AU - Martinek, Tamás TI - A Foldamer-Dendrimer Conjugate Neutralizes Synaptotoxic Beta-Amyloid Oligomers JF - PLOS ONE J2 - PLOS ONE VL - 7 PY - 2012 IS - 7 PG - 17 SN - 1932-6203 DO - 10.1371/journal.pone.0039485 UR - https://m2.mtmt.hu/api/publication/2034805 ID - 2034805 N1 - Funding Agency and Grant Number: EU FP7 [HEALTH-F2-2007-201159, HEALTH-F2-2007-211696]; COST [CM0803]; Hungarian Research Foundation [NK81371, PD83581, PD83600, K68152]; Hungarian Academy of Sciences, Lendulet programme\n Funding text: This work was supported by the EU FP7 (HEALTH-F2-2007-201159, HEALTH-F2-2007-211696 and COST CM0803) (http://cordis.europa.eu/fp7/home_en.html); the Hungarian Research Foundation (NK81371, PD83581, PD83600 and K68152) (http://www.otka.hu/); and the Hungarian Academy of Sciences, Lendulet programme (http://mta.hu/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.\n Department of Medical Chemistry, University of Szeged, Szeged, Hungary Institute of Pharmaceutical Chemistry, University of Szeged, Szeged, Hungary Bay Zoltán Foundation for Applied Research - BAYGEN, Szeged, Hungary Department of Physical Chemistry and Materials Science, University of Szeged, Szeged, Hungary Cited By :31 Export Date: 24 April 2020 Correspondence Address: Martinek, T. A.; Institute of Pharmaceutical Chemistry, University of Szeged, Szeged, Hungary; email: martinek@pharm.u-szeged.hu Chemicals/CAS: amyloid beta protein, 109770-29-8; Amyloid beta-Peptides; Dendrimers CAplus AN 2012:1144372; MEDLINE PMID: 22859942 (Journal; Article; Research Support, Non-U.S. Gov't); AB - 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.

 LA - English DB - MTMT ER - TY - JOUR AU - Martinek, Tamás AU - Fülöp, Ferenc TI - Peptidic foldamers: ramping up diversity JF - CHEMICAL SOCIETY REVIEWS J2 - CHEM SOC REV VL - 41 PY - 2012 IS - 2 SP - 687 EP - 702 PG - 16 SN - 0306-0012 DO - 10.1039/c1cs15097a UR - https://m2.mtmt.hu/api/publication/1842290 ID - 1842290 N1 - Funding Agency and Grant Number: Hungarian Research FoundationOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [NK81371, K83882, TAMOP-4.2.1/B-09/1/KONV-2010-0005]; COSTEuropean Cooperation in Science and Technology (COST) [CM0803]; Janos Bolyai FellowshipHungarian Academy of Sciences; HAS [LP2011-009/2011] Funding text: We thank the Hungarian Research Foundation (NK81371 and K83882), TAMOP-4.2.1/B-09/1/KONV-2010-0005 and COST (CM0803) for financial support. T.A.M. acknowledges the Janos Bolyai Fellowship and the "Lendulet'' programme (LP2011-009/2011) from the HAS. CAplus AN 2012:19612; MEDLINE PMID: 21769415 (Journal; General Review; Article; Research Support, Non-U.S. Gov't; Review); AB - 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). LA - English DB - MTMT ER - TY - JOUR AU - Jones, C J AU - Béni, Szabolcs AU - Limtiaco, J F K AU - Langeslay, D J AU - Larive, C K TI - Heparin characterization:challenges and solutions JF - ANNUAL REVIEW OF ANALYTICAL CHEMISTRY J2 - ANNU REV ANAL CHEM VL - 4 PY - 2011 SP - 439 EP - 465 PG - 27 SN - 1936-1327 DO - 10.1146/annurev-anchem-061010-113911 UR - https://m2.mtmt.hu/api/publication/2316260 ID - 2316260 N1 - Megjegyzés-21981490 Chemicals/CAS: heparin, 37187-54-5, 8057-48-5, 8065-01-8, 9005-48-5; Heparin, 9005-49-6 LA - English DB - MTMT ER -