DomenicaMusumeci
a,b
; Samee Ullah
c
;Aamer Ikram
c
; Giovanni N. Roviello
b*
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Nucleopeptides are a class of molecules with numerous applications
in the field of therapy, diagnostics and biomaterials development. Despite
their nucleobase-decorated nature, their binding with natural nucleic acid
targets does not necessarily involve all nucleopeptide bases, as we showed in
this study. Here, we present a CD study on the interaction of a
dithymine-functionalized tetra-L-serine with a homoadenine DNA (dA
12
)
reporting an interpretation of the experimental data in light of our computational
studies based on molecular docking and molecular dynamics (MD), as well as computer-assisted
CD interpretation and simulation of the predicted complex structure. The stoichiometry
of the complex, emerged by CD titration, accounted for a 1:2 T:A ratio. Hence,
we supposed that binding did not involve a full pairing of the complementary
bases but a partial thymines engagement. This hypothesis was sustained by the
docking and MD simulations performed on the selected ligand and the
complementary target of DNA and RNA, used for comparison. The nucleopeptide bound
the DNA through a single A-T recognition involving complementary base-pairing, as
well as some interactions between its backbone (and in particular L-serine OH) with
the nucleic acid. Overall, this
confirmed that nucleopeptides can interact with nucleic acids leaving some of
their nucleobases free for further interactions with other biomolecules or for
crosslinking in supramolecular structures in aqueous solution. Nevertheless,
even though no typical DNA secondary structure is formed after
nucleopeptide-binding, this ligand is able to induce a higher degree of
structuration in the random deoxyoligonucleotide
target as evidenced by CD, MD and CD simulation