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  - 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  -