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Side-Chain Proline-Based Polymers as Effective Inhibitors for In Vitro Aggregation of Insulin
journal contribution
posted on 2020-08-05, 22:03 authored by Pooja Ghosh, Avisek Bera, Anwesha Ghosh, Punyasloke Bhadury, Priyadarsi DeInsulin
fibril formation is considered as the hallmark of several
debilitating pathological conditions. To develop effective therapeutics
that are able to control the amyloidogenesis process and inhibit fibril
formation, herein we have designed a side-chain proline (Pro)-based
homopolymer and block copolymers through the reversible addition–fragmentation
chain transfer (RAFT) polymerization technique and further explored
their obligatory role in the in vitro insulin fibrillation process.
Using a variety of biophysical tools, including turbidity measurements,
thioflavin T (ThT) fluorescence kinetics, tyrosine (Tyr) fluorescence
study, Nile red (NR) fluorescence assay, dynamic light scattering
(DLS) study, circular dichroism (CD) measurements, and isothermal
titration calorimetry (ITC) techniques, we demonstrated that Pro-based
polymers can significantly inhibit the insulin fibrillation process.
Among them, the Pro-based homopolymer acts as the most potent inhibitor
of insulin fibrillation as confirmed by ThT assay, CD study, and transmission
electron microscopic (TEM) analysis. Tyrosine fluorescence measurements
and NR fluorescence assay revealed that hydrophobic interactions are
the crucial factor that mainly controls the inhibition process. Apart
from hydrophobic interactions, polar interactions may also be responsible
for the inhibition process as evaluated by ITC study.