Neuroblastoma Homing Peptide Screening Using Unrefined Homology Structure of Norepinephrine Transporter

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62156489%3A43210%2F16%3A43910235" target="_blank" >RIV/62156489:43210/16:43910235 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216305:26620/16:PU122772

Výsledek na webu

<a href="https://mnet.mendelu.cz/mendelnet2016/mnet_2016_full.pdf" target="_blank" >https://mnet.mendelu.cz/mendelnet2016/mnet_2016_full.pdf</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Neuroblastoma Homing Peptide Screening Using Unrefined Homology Structure of Norepinephrine Transporter

Popis výsledku v původním jazyce

The norepinephrine transporter (hNET) is a potential target for many antidepressants and for neuroblastoma therapeutics. The entrance channel of hNET and also dopamine transporter (DAT) serve as candidate site for targeting by large peptides e.g. α-helix-based. Targeting peptides, also known as homing peptides, are used to direct the delivery of cargo to specific cell types. Peptides of known secondary structures such as α-helix and β-sheet have predictable and stable folding. In this study, approx. 27 peptides, with predictable secondary structures, were evaluated by 20 dockings predictions on unrefined hNET homology model and DAT crystal structure using molecular mechanics (total ~1080 models). As anticipated, peptide size was detrimental for docking in channel space, whereas peptide isoelectrics point did not affect docking. Peptide's initial non-bonded energy affected docking while overall peptide free energy and initial electrostatic energy did not. Two α-helices showed favorable docking in channel of hNET; namely, GASNGINAYL and SLWERLAYGI with binding energy of -106.2 kJ/mol and -128.6 kJ/mol, respectively. Prior to in vitro and in vivo applications, future work will focus on development of refined accurate model of hNET and application of solvated docking (in presence of water). This study provides new insight to the development of helix-based therapeutic peptides.

Název v anglickém jazyce

Neuroblastoma Homing Peptide Screening Using Unrefined Homology Structure of Norepinephrine Transporter

Popis výsledku anglicky

The norepinephrine transporter (hNET) is a potential target for many antidepressants and for neuroblastoma therapeutics. The entrance channel of hNET and also dopamine transporter (DAT) serve as candidate site for targeting by large peptides e.g. α-helix-based. Targeting peptides, also known as homing peptides, are used to direct the delivery of cargo to specific cell types. Peptides of known secondary structures such as α-helix and β-sheet have predictable and stable folding. In this study, approx. 27 peptides, with predictable secondary structures, were evaluated by 20 dockings predictions on unrefined hNET homology model and DAT crystal structure using molecular mechanics (total ~1080 models). As anticipated, peptide size was detrimental for docking in channel space, whereas peptide isoelectrics point did not affect docking. Peptide's initial non-bonded energy affected docking while overall peptide free energy and initial electrostatic energy did not. Two α-helices showed favorable docking in channel of hNET; namely, GASNGINAYL and SLWERLAYGI with binding energy of -106.2 kJ/mol and -128.6 kJ/mol, respectively. Prior to in vitro and in vivo applications, future work will focus on development of refined accurate model of hNET and application of solvated docking (in presence of water). This study provides new insight to the development of helix-based therapeutic peptides.

Druh

D - Stať ve sborníku

CEP obor

CF - Fyzikální chemie a teoretická chemie

OECD FORD obor

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Projekt

<a href="/cs/project/NV15-28334A" target="_blank" >NV15-28334A: Vliv metalothioneinů na vazbu platinových cytostatik na DNA v nádorových buňkách</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název statě ve sborníku

MendelNet 2016: Proceedings of International PhD Students Conference

ISBN

978-80-7509-443-8

ISSN

—

e-ISSN

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Počet stran výsledku

6

Strana od-do

983-988

Název nakladatele

Mendelova univerzita v Brně

Místo vydání

Brno

Místo konání akce

Brno

Datum konání akce

9. 11. 2016

Typ akce podle státní příslušnosti

EUR - Evropská akce

Kód UT WoS článku

000392968500176