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Funding text: This work was supported by the Hungarian Academy of Sciences, Lendulet program (LP-2011-009) and GINOP-2.3.3-15-2016-00010. E. W. thanks the Postdoctoral Fellowship Program 2014 of the Hungarian Academy of Sciences.
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Peripheral cyclic β-amino acids balance the stability and edge-protection of β-sandwiches
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Engineering water-soluble stand-alone beta-sandwich mimetics is a current challenge because of the difficulties associated with tailoring long-range interactions. In this work, single cis-(1R,2S)-2-aminocyclohexanecarboxylic acid mutations were introduced into the edge strands of the eight-stranded beta-sandwich mimetic structures from the betabellin family. Temperature-dependent NMR and CD measurements, together with thermodynamic analyses, demonstrated that the modified peripheral strands exhibited an irregular and partially disordered structure but were able to exert sufficient shielding on the hydrophobic core to retain the predominantly beta-sandwich structure. Although the frustrated interactions decreased the free energy of unfolding, the temperature of the maximum stabilities increased to or remained at physiologically relevant temperatures. We found that the irregular peripheral strands were able to prevent edge-to-edge association and fibril formation in the aggregation-prone model. These findings establish a beta-sandwich stabilization and aggregation inhibition approach, which does not interfere with the pillars of the peptide bond or change the net charge of the peptide.
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Gyógyszeranalitikai Intézet (SZTE / GYTK); MTA-SZTE Biomimetikus Rendszerek Kutatócsoport (SZTE / SZAOK / OVI); Orvosi Vegytani Intézet (SZTE / SZAOK)
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<div class="JournalArticle Publication short-list"> <div class="authors"> <span class="author-name" mtid="10033721"> <a href="/gui2/?type=authors&mode=browse&sel=10033721" target="_blank">Olajos, G</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10001147"> <a href="/gui2/?type=authors&mode=browse&sel=10001147" target="_blank">Hetenyi, A</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10027663"> <a href="/gui2/?type=authors&mode=browse&sel=10027663" target="_blank">Weber, E</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10038001"> <a href="/gui2/?type=authors&mode=browse&sel=10038001" target="_blank">Szogi, T</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10000567"> <a href="/gui2/?type=authors&mode=browse&sel=10000567" target="_blank">Fulop, L</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10001168"> <a href="/gui2/?type=authors&mode=browse&sel=10001168" target="_blank">Martinek, TA ✉</a> </span> <span class="author-type"> </span> </div ><div class="title"><a href="/gui2/?mode=browse¶ms=publication;3399101" mtid="3399101" target="_blank">Peripheral cyclic β-amino acids balance the stability and edge-protection of β-sandwiches</a></div> <div class="pub-info"> <span class="journal-title">ORGANIC & BIOMOLECULAR CHEMISTRY</span> <span class="journal-volume">16</span> : <span class="journal-issue">30</span> <span class="page"> pp. 5492-5499. , 8 p. </span> <span class="year">(2018)</span> </div> <div class="pub-end"><div class="identifier-list"> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.1039/c8ob01322e" target="_blank" href="https://doi.org/10.1039/c8ob01322e"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000440580100017" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000440580100017"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85051086566" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85051086566"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="30024580" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=30024580&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_CLOSED" title=" Zárt "> <a style="color:black" title="13944" target="_blank" href="http://publicatio.bibl.u-szeged.hu/13944"> SZTE Publicatio </a> </span> </span> </div> <div class="short-pub-prop-list"> <span class="deleted-record">Zárolt</span> <span class="short-pub-mtid"> Közlemény:3399101 </span> <span class="status-holder"><span class="status-data status-VALIDATED"> Egyeztetett </span></span> <span class="pub-core">Forrás Idéző </span> <span class="pub-type">Folyóiratcikk (Szakcikk ) </span> <!-- && !record.category.scientific --> <span class="pub-category">Tudományos</span> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 3</span> | Független: 3 | Függő: 0 | Nem jelölt: 0 | WoS jelölt: 2 | Scopus jelölt: 2 | WoS/Scopus jelölt: 2 | DOI jelölt: 2 </div> </div> </div> </div><div class="JournalArticle Publication long-list">
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Gyógyszerésztudományi Kar">GYTK</span>/Gyógyszeranalitikai Intézet; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Orvosi Vegytani Intézet">OVI</span>/MTA-SZTE Biomimetikus Rendszerek Kutatócsoport</span>
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/Orvosi Vegytani Intézet</span>
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Gyógyszerésztudományi Kar">GYTK</span>/Gyógyszeranalitikai Intézet; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Orvosi Vegytani Intézet">OVI</span>/MTA-SZTE Biomimetikus Rendszerek Kutatócsoport</span>
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<div class="title"><a href="/gui2/?mode=browse¶ms=publication;3399101" target="_blank">Peripheral cyclic β-amino acids balance the stability and edge-protection of β-sandwiches</a></div> <div> <span class="journal-title">ORGANIC & BIOMOLECULAR CHEMISTRY</span>
<span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/1477-0520">1477-0520</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1477-0539">1477-0539</a>)</span>:
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<div class="funder"> Szerkezetvizsgálati infrastruktúra fejlesztése önszerveződő rendszerek alkalmazásaihoz: atomi szi...(GINOP-2.3.3-15-2016-00010) </div>
<div class="lastModified">Utolsó módosítás: 2024.01.29. 10:50 Belházyné Szombathelyi Ágnes (SZTE admin5)
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<div class="lockedBy">Ideiglenesen zárolva 2024.03.11. 18:47 Pécsi Éva (MTMT Közp 3, admin)
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<pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Megjegyzés</u>: Funding text: This work was supported by the Hungarian Academy of Sciences, Lendulet program (LP-2011-009) and GINOP-2.3.3-15-2016-00010. E. W. thanks the Postdoctoral Fellowship Program 2014 of the Hungarian Academy of Sciences.</pre>
</div></div>