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Probing the Assembly of HDL Mimetic, Drug Carrying Nanoparticles Using Intrinsic Fluorescence
Raut, Sangram Garud, Ashwini Nagarajan, Bhavanai Sabnis, Nirupama Remaley, Alan Fudala, Rafal Gryczynski, Ignacy Gryczynski, Zygmunt Dzyuba, Sergei V. Borejdo, Julian
Raut, Sangram
Garud, Ashwini
Nagarajan, Bhavanai
Sabnis, Nirupama
Remaley, Alan
Fudala, Rafal
Gryczynski, Ignacy
Gryczynski, Zygmunt
Dzyuba, Sergei V.
Borejdo, Julian
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Publisher
ASPET
Date
2020-03-16
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Abstract
Reconstituted high-density lipoprotein (HDL) containing apolipoprotein A-I (Apo A-I) mimics the structure and function of endogenous (human plasma) HDL due to its function and potential therapeutic utility in atherosclerosis, cancer, neurodegenerative diseases, and inflammatory diseases. Recently, a new class of HDL mimetics has emerged, involving peptides with amino acid sequences that simulate the the primary structure of the amphipathic alpha helices within the Apo A-I protein. The findings reported in this communication were obtained using a similar amphiphilic peptide (modified via conjugation of a myristic acid residue at the amino terminal aspartic acid) that self-assembles (by itself) into nanoparticles while retaining the key features of endogenous HDL. The studies presented here involve the macromolecular assembly of the myristic acid conjugated peptide (MYR-5A) into nanomicellar structures and its characterization via steady-state and time-resolved fluorescence spectroscopy. The structural differences between the free peptide (5A) and MYR-5A conjugate were also probed, using tryptophan fluorescence, Förster resonance energy transfer (FRET), dynamic light scattering, and gel exclusion chromatography. To our knowledge, this is the first report of a lipoprotein assembly generated from a single ingredient and without a separate lipid component. The therapeutic utility of these nanoparticles (due to their capablity to incorporate a wide range of drugs into their core region for targeted delivery) was also investigated by probing the role of the scavenger receptor type B1 in this process.
Contents
Subject
Apolipoprotein-A-I
Protein Secondary Structure
Synthetic Peptide Analogs
High-Density-Lipoproteins
Cholesterol Efflux
Antiinflammatory Properties
Poor-Prognosis
Delivery
Atherosclerosis
Doxorubicin
Protein Secondary Structure
Synthetic Peptide Analogs
High-Density-Lipoproteins
Cholesterol Efflux
Antiinflammatory Properties
Poor-Prognosis
Delivery
Atherosclerosis
Doxorubicin
Subject(s)
Research Projects
Organizational Units
Journal Issue
Genre
Description
Format
Department
Physics and Astronomy
Chemistry and Biochemistry
Chemistry and Biochemistry