Neuroblastoma homing peptide screening using unrefined homology structure of norepinephrine transporter

článek ve sborníku ve WoS nebo Scopus

angličtina

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 peptideisoelectrics 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.

targeted therapy; norepinephrine transporter; homing peptide; molecular mechanics; docking

HADDAD, Y.; HEGER, Z.; ADAM, V.

12. 12. 2016

Brno, Czech Republic

Brno

978-80-7509-443-8

MendelNet 2016

983

988

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