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001-es BibID:	BIBFORM105453
035-os BibID:	(cikkazonosító)2559 (WOS)000904144700001 (Scopus)85144901772
Első szerző:	Kovács Tamás (általános orvos)
Cím:	Cyclodextrins : Only Pharmaceutical Excipients or Full-Fledged Drug Candidates? / Kovacs Tamas, Nagy Peter, Panyi Gyorgy, Szente Lajos, Varga Zoltan, Zakany Florina
Dátum:	2022
ISSN:	1999-4923
Megjegyzések:	Cyclodextrins, representing a versatile family of cyclic oligosaccharides, have extensive pharmaceutical applications due to their unique truncated cone-shaped structure with a hydrophilic outer surface and a hydrophobic cavity, which enables them to form non-covalent host?guest inclusion complexes in pharmaceutical formulations to enhance the solubility, stability and bioavailability of numerous drug molecules. As a result, cyclodextrins are mostly considered as inert carriers during their medical application, while their ability to interact not only with small molecules but also with lipids and proteins is largely neglected. By forming inclusion complexes with cholesterol, cyclodextrins deplete cholesterol from cellular membranes and thereby influence protein function indirectly through alterations in biophysical properties and lateral heterogeneity of bilayers. In this review, we summarize the general chemical principles of direct cyclodextrin?protein interactions and highlight, through relevant examples, how these interactions can modify protein functions in vivo, which, despite their huge potential, have been completely unexploited in therapy so far. Finally, we give a brief overview of disorders such as Niemann?Pick type C disease, atherosclerosis, Alzheimer's and Parkinson's disease, in which cyclodextrins already have or could have the potential to be active therapeutic agents due to their cholesterol-complexing or direct protein-targeting properties.
Tárgyszavak:	Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Pharmaceutics. - 14 (2022), p. 1-38. -
További szerzők:	Nagy Péter (1971-) (biofizikus) Panyi György (1966-) (biofizikus) Szente Lajos (1951-) (vegyész) Varga Zoltán (1969-) (biofizikus, szakfordító) Zákány Florina (1989-) (általános orvos)
Pályázati támogatás:	ANN133421 OTKA K138075 OTKA FK143400 OTKA K143071 OTKA K132906 OTKA UNKP?22?4?II?DE?69 Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM107302
035-os BibID:	(scopus)85141712265 (wos)000882982200001
Első szerző:	Reddiar, Sanjeevini Babu
Cím:	A Biodistribution Study of the Radiolabeled Kv1.3-Blocking Peptide DOTA-HsTX1[R14A] Demonstrates Brain Uptake in a Mouse Model of Neuroinflammation / Reddiar Sanjeevini Babu, de Veer Michael, Paterson Brett M., Sepehrizadeh Tara, Wai Dorothy C. C., Csoti Agota, Panyi Gyorgy, Nicolazzo Joseph A., Norton Raymond S.
Dátum:	2023
ISSN:	1543-8384 1543-8392
Megjegyzések:	The voltage-gated potassium channel Kv1.3 regulates the pro-inflammatory function of microglia and is highly expressed in the post-mortem brains of individuals with Alzheimer's and Parkinson's diseases. HsTX1[R14A] is a selective and potent peptide inhibitor of the Kv1.3 channel (IC50 ? 45 pM) that has been shown to decrease cytokine levels in a lipopolysaccharide (LPS)-induced mouse model of inflammation. Central nervous system exposure to HsTX1[R14A] was previously detected in this mouse model using liquid chromatography with tandem mass spectrometry, but this technique does not report on the spatial distribution of the peptide in the different brain regions or peripheral organs. Herein, the in vivo distribution of a [64Cu]Cu-labeled DOTA conjugate of HsTX1[R14A] was observed for up to 48 h by positron emission tomography (PET) in mice. After subcutaneous administration to untreated C57BL/6J mice, considerable uptake of the radiolabeled peptide was observed in the kidney, but it was undetectable in the brain. Biodistribution of a [68Ga]Ga-DOTA conjugate of HsTX1[R14A] was then investigated in the LPS-induced mouse model of neuroinflammation to assess the effects of inflammation on uptake of the peptide in the brain. A control peptide with very weak Kv1.3 binding, [68Ga]Ga-DOTA-HsTX1[R14A,Y21A,K23A] (IC50 ? 6 ?M), was also tested. Significantly increased uptake of [68Ga]Ga-DOTA-HsTX1[R14A] was observed in the brains of LPS-treated mice compared to mice treated with control peptide, implying that the enhanced uptake was due to increased Kv1.3 expression rather than simply increased blood?brain barrier disruption. PET imaging also showed accumulation of [68Ga]Ga-DOTA-HsTX1[R14A] in inflamed joints and decreased clearance from the kidneys in LPS-treated mice. These biodistribution data highlight the potential of HsTX1[R14A] as a therapeutic for the treatment of neuroinflammatory diseases mediated by overexpression of Kv1.3.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Biodistribution Central nervous system Inflammation Peptides and proteins Rodent models
Megjelenés:	Molecular Pharmaceutics. - 20 : 1 (2023), p. 255-266. -
További szerzők:	de Veer, Michael Paterson, Brett M. Sepehrizadeh, Tara Wai, Dorothy C. C. Csóti Ágota (1989-) (biológus) Panyi György (1966-) (biofizikus) Nicolazzo, Joseph A. Norton, Raymond S.
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