CCL

Összesen 2 találat.
#/oldal:
Részletezés:
Rendezés:

1.

001-es BibID:BIBFORM094509
035-os BibID:(Cikkazonosító)31877 (WOS)000381563400001 (Scopus)84983354675
Első szerző:Dobó József
Cím:MASP-3 is the exclusive pro-factor D activator in resting blood : the lectin and the alternative complement pathways are fundamentally linked / József Dobó, Dávid Szakács, Gábor Oroszlán, Elod Kortvely, Bence Kiss, Eszter Boros, Róbert Szász, Péter Závodszky, Péter Gál, Gábor Pál
Dátum:2016
ISSN:2045-2322
Megjegyzések:MASP-3 was discovered 15 years ago as the third mannan-binding lectin (MBL)-associated serine protease of the complement lectin pathway. Lacking any verified substrate its role remained ambiguous. MASP-3 was shown to compete with a key lectin pathway enzyme MASP-2 for MBL binding, and was therefore considered to be a negative complement regulator. Later, knock-out mice experiments suggested that MASP-1 and/or MASP-3 play important roles in complement pro-factor D (pro-FD) maturation. However, studies on a MASP-1/MASP-3-deficient human patient produced contradicting results. In normal resting blood unperturbed by ongoing coagulation or complement activation, factor D is present predominantly in its active form, suggesting that resting blood contains at least one pro-FD activating proteinase that is not a direct initiator of coagulation or complement activation. We have recently showed that all three MASPs can activate pro-FD in vitro. In resting blood, however, using our previously evolved MASP-1 and MASP-2 inhibitors we proved that neither MASP-1 nor MASP-2 activates pro-FD. Other plasma proteinases, particularly MASP-3, remained candidates for that function. For this study we evolved a specific MASP-3 inhibitor and unambiguously proved that activated MASP-3 is the exclusive pro-FD activator in resting blood, which demonstrates a fundamental link between the lectin and alternative pathways.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
MASP-3
factor D
Megjelenés:Scientific Reports. - 6 (2016), p. 1-12. -
További szerzők:Szakács Dávid Oroszlán Gábor Kortvely, Elod Kiss Bence Boros Eszter Szász Róbert (1972-) (belgyógyász, haematológus) Závodszky Péter Gál Péter Pál Gábor
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

2.

001-es BibID:BIBFORM094508
035-os BibID:(WoS)000470656500020 (Scopus)85066156398
Első szerző:Szakács Dávid
Cím:Novel MASP-2 inhibitors developed via directed evolution of human TFPI1 are potent lectin pathway inhibitors / Dávid Szakács, Andrea Kocsis, Róbert Szász, Péter Gál, Gábor Pál
Dátum:2019
ISSN:0021-9258 1083-351X
Megjegyzések:The lectin pathway (LP) of the complement system is an important antimicrobial defense mechanism, but it also contributes significantly to ischemia reperfusion injury (IRI) associated with myocardial infarct, stroke, and several other clinical conditions. Mannan-binding lectin-associated serine proteinase 2 (MASP-2) is essential for LP activation, and therefore, it is a potential drug target. We have previously developed the first two generations of MASP-2 inhibitors by in vitro evolution of two unrelated canonical serine proteinase inhibitors. These inhibitors were selective LP inhibitors, but their nonhuman origin rendered them suboptimal lead molecules for drug development. Here, we present our third-generation MASP-2 inhibitors that were developed based on a human inhibitor scaffold. We subjected the second Kunitz domain of human tissue factor pathway inhibitor 1 (TFPI1 D2) to directed evolution using phage display to yield inhibitors against human and rat MASP-2. These novel TFPI1-based MASP-2 inhibitor (TFMI-2) variants are potent and selective LP inhibitors in both human and rat serum. Directed evolution of the first Kunitz domain of TFPI1 had already yielded the potent kallikrein inhibitor, Kalbitor? (ecallantide), which is an FDA-approved drug to treat acute attacks of hereditary angioedema. Like hereditary angioedema, acute IRI is also related to the uncontrolled activation of a specific plasma serine proteinase. Therefore, TFMI-2 variants are promising lead molecules for drug development against IRI.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
MASP
TFPI1
MASP-2 inhibitor
Megjelenés:Journal Of Biological Chemistry. - 294 : 20 (2019), p. 8227-8237. -
További szerzők:Kocsis Andrea Szász Róbert (1972-) (belgyógyász, haematológus) Gál Péter Pál Gábor
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Rekordok letöltése1