Optimization of Amino Acid Sequence of Fmoc-Dipeptides for Interaction with Lipid Membranes
Autor
Argudo, Pablo G.
Contreras-Montoya, Rafael
Álvarez de Cienfuegos, Luis
Camacho, Luis
Giner-Casares, Juan J.
Martín-Romero, M.T.
Editor
ACS PublicationsFecha
2019Materia
DipéptidosAutoensamblaje
Nanotecnología
Monocapas
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Fmoc-dipeptides appear as highly relevant
building blocks in smart hydrogels and nanovehicles for
biological applications. The interactions of the Fmocdipeptides
with the cell membrane determine the efficiency
of the nanomaterials based on the Fmoc-dipeptides’ internalization
of nanovehicles for drug delivery. Here, we aim to
understand the interplay of the interactions between the
Fmoc-dipeptides and a phospholipid surface as a function of
the amino acid sequence. The DMPA (1,2-dimyristoyl-snglycero-
3-phosphate) phospholipid in Langmuir monolayers
was used as a model cell surface. A set of seven derivatives of
Fmoc-dipeptides with a broad range of hydrophobicity were
included. Mixed monolayers composed of DMPA/Fmoc-dipeptides in an equimolar ratio were built and characterized in situ at
the air/water interface. Surface pressure−molecular area isotherms (π−A), Brewster angle microscopy (BAM), and UV−vis
reflection spectroscopy (ΔR) were combined to provide a holistic picture of the interactions of the Fmoc-dipeptide with the
phospholipid molecules. An increase in the hydrophobicity led to enhanced interaction of the Fmoc-dipeptide and DMPA
molecules. The compression of the mixed monolayer could displace a significant fraction of the Fmoc-dipeptide from the
monolayer. High hydrophobicity promoted self-assembly of the Fmoc-dipeptides over interaction with the phospholipid surface.
The interplay of these two phenomena was analyzed as a function of the amino acid sequence of the Fmoc-dipeptides. The
toxicity effect of Fmoc-FF could be observed and detailed at the molecular level. This study suggests that the adjustment of the
hydrophobicity of the Fmoc-dipeptides within a defined range might optimize their efficiency for interaction with the lipid
membranes. A semiquantitative guide for the chemical design of Fmoc-dipeptides for biological applications is proposed herein.