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001-es BibID:	BIBFORM062511
Első szerző:	Fehér Krisztina (vegyész)
Cím:	Probing pattern and dynamics of disulfide bridges using synthesis and NMR of an ion channel blocker peptide toxin with multiple diselenide bonds / Krisztina Fehér, István Timári, Kinga Rákosi, János Szolomájer, Tünde Z. Illyés, Ádám Bartók, Zoltán Varga, György Panyi, Gábor K. Tóth, Katalin E. Kövér
Dátum:	2016
ISSN:	2041-6520 2041-6539
Megjegyzések:	Anuroctoxin (AnTx), a 35-amino-acid scorpion toxin containing four disulfide bridges, is a high affinity blocker of the voltage-gated potassium channel Kv1.3, but also blocks Kv1.2. To improve potential therapeutic use of the toxin, we have designed a double substituted analog, [N17A/F32T]-AnTx, which showed comparable Kv1.3 affinity to the wild-type peptide, but also a 2500-fold increase in the selectivity for Kv1.3 over Kv1.2. In the present study we have achieved the chemical synthesis of a Sec-analog in which all cysteine (Cys) residues have been replaced by selenocysteine (Sec) forming four diselenide bonds. To the best of our knowledge this is the first time to replace, by chemical synthesis, all disulfide bonds with isosteric diselenides in a peptide/protein. Gratifyingly, the key pharmacological properties of the Sec-[N17A/F32T]-AnTx are retained since the peptide is functionally active. We also propose here a combined experimental and theoretical approach including NOE- and 77Se-based NMR supplemented by MD simulations for conformational and dynamic characterization of the Sec-[N17A/F32T]-AnTx. Using this combined approach allowed us to attain unequivocal assignment of all four diselenide bonds and supplemental MD simulations allowed characterization of the conformational dynamics around each disulfide/diselenide bridge.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban peptide toxin ion channels disulfide bridge
Megjelenés:	Chemical Science 7 (2016), p. 2666-2673. -
További szerzők:	Timári István (1989-) (vegyész) Rákosi Kinga Szolomájer János Illyés Tünde Zita (1970-) (kémia-fizika szakos tanár) Bartók Ádám (1984-) (biotechnológus) Varga Zoltán (1969-) (biofizikus, szakfordító) Panyi György (1966-) (biofizikus) Tóth Gábor K. Kövér Katalin, E. (1956-2023) (vegyész)
Pályázati támogatás:	TAMOP-4.2.2/A-11/1/KONV-2012-0025 TÁMOP TAMOP-4.2.2/A-11/1/KONV-2012-0035 TÁMOP OTKA K 75904 OTKA OTKA NK 101337 OTKA OTKA K 105459 OTKA KTIA_NAP_13-2-2015?0009 Egyéb KTIA_13_NAP-A-III/8 Egyéb
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001-es BibID:	BIBFORM103334
035-os BibID:	(WOS)000555801800006 (Scopus)85089285156
Első szerző:	Leone, Loredana
Cím:	Acid-catalyzed proton exchange as a novel approach for relaxivity enhancement in Gd-HPDO3A-like complexes / Loredana Leone, Mariangela Boccalon, Giuseppe Ferrauto, István Fábián, Zsolt Baranyai, Lorenzo Tei
Dátum:	2020
ISSN:	2041-6520 2041-6539
Megjegyzések:	A current challenge in medical diagnostics is how to obtain high MRI relaxation enhancement using Gd-III-based contrast agents (CAs) containing the minimum concentration of Gd(III)ions. We report that in GdHPDO3A-like complexes a primary amide group located in close proximity to the coordinated hydroxyl group can provide a strong relaxivity enhancement at slightly acidic pH. A maximum relaxivity ofr(1)= 9.8 mM(-1)s(-1)(20 MHz, 298 K) at acidic pH was achieved, which is more than double that of clinically approved MRI contrast agents under identical conditions. This effect was found to strongly depend on the number of amide protons,i.e.it decreases with a secondary amide group and almost completely vanishes with a tertiary amide. This relaxivity enhancement is attributed to an acid-catalyzed proton exchange process between the metal-coordinated OH group, the amide protons and second sphere water molecules. The mechanism and kinetics of the corresponding H(+)assisted exchange process are discussed in detail and a novel simultaneous double-site proton exchange mechanism is proposed. Furthermore,H-1 and(17)O NMR relaxometry, Chemical Exchange Saturation Transfer (CEST) on the corresponding Eu(III)complexes, and thermodynamic and kinetic studies are reported. These highlight the optimal physico-chemical properties required to achieve high relaxivity with this series of Gd-III-complexes. Thus, proton exchange provides an important opportunity to enhance the relaxivity of contrast agents, providing that labile protons close to the paramagnetic center can contribute.
Tárgyszavak:	Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Chemical Science. - 11 : 30 (2020), p. 7829-7835. -
További szerzők:	Boccalon, Mariangela Ferrauto, Giuseppe Fábián István (1956-) (vegyész) Baranyai Zsolt Tei, Lorenzo
Pályázati támogatás:	NKFIH-K-124983 Egyéb
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