Angewandte
Communications
Chemie
Molecular Recognition
A Programmable Signaling Molecular Recognition Nanocavity
Abstract: Inspired by biosystems, a process is proposed for
preparing next-generation artificial polymer receptors with
molecular recognition abilities capable of programmable site-
directed modification following construction of nanocavities to
provide multi-functionality. The proposed strategy involves
strictly regulated multi-step chemical modifications: 1) fabri-
cation of scaffolds by molecular imprinting for use as
molecular recognition fields possessing reactive sites for
further modifications at pre-determined positions, and 2) con-
jugation of appropriate functional groups with the reactive sites
by post-imprinting modifications to develop programmed
functionalizations designed prior to polymerization, allowing
independent introduction of multiple functional groups. The
proposed strategy holds promise as a reliable, affordable, and
versatile approach, facilitating the emergence of polymer-
based artificial antibodies bearing desirable functions that are
beyond those of natural antibodies.
In this context, synthetic materials capable of molecular
recognition and additional bio-relevant functions have been
attracting significant attention as substitutes for naturally
[3]
occurring functionalized proteins. In particular, molecularly
imprinted polymers (MIPs) are well-known as artificial
polymer receptors and have been used as affinity separation
media, molecular recognition elements for sensors, and
[4]
specific target-capturing materials in ligand binding assays.
Molecular imprinting involves a template molecule inducing
the formation of nanocavities capable of molecular recog-
nition by co-polymerizing crosslinker(s) and co-monomer(s)
in the presence of functional monomer–template molecule
complexes. Templating involves covalent linkages and/or
noncovalent interactions, and the template molecule is
either the target molecule or a derivative. After polymeri-
zation, the template molecule is removed, resulting in
molecularly imprinted cavities complementary in shape,
size, and alignment of functional groups suitable for rebinding
the target molecule and/or its structurally related derivatives.
Because of the simplicity of the process, MIPs have a good
reputation as functional materials, but the functionality on
most MIPs reported to date is rather simple and far from the
complex functions of natural proteins.
P
roteins play important biological roles, such as the trans-
portation of molecules, the transduction of stimuli-responsive
signals, and the mediation of catalysis involved in metabolism
and biosynthesis. These functions are made possible by post-
biosynthetic processes called posttranslational modification,
that is, the formation of more complex functionalized adducts
Recently, we reported a biomimetic molecular imprinting
process for the creation of new classes of synthetic multi-
functional materials for small molecules capable of molecular
recognition, signal transduction, and photoresponsiveness.
These materials are acquired by site-directed post-polymer-
ization modifications at predetermined positions within the
imprinted cavities (post-imprinting modification, PIM), in
which prosthetic groups are introduced into these cavities
either covalently or non-covalently to improve binding
activity, thus mimicking post-translational modification in
[
1]
by the conjugation of non-protein groups. This strategy is
advantageous because the biosynthetic process for fabricating
apo-type scaffold proteins and the subsequent modification
process for yielding holo-type functionalized proteins pro-
ceed independently under their respectively optimized con-
ditions, enabling the preparation of complicated and sophis-
ticated functional proteins. The finely tuned performance of
conjugated proteins and other function-acquired proteins are
of great interest for applications to various life science and
[2]
[5]
bio-production processes. However, these proteins are not
sufficiently stable for use in industrial applications, and their
bio-production is problematic from the standpoint of cost and
quality control.
biosystems. This modification can help achieve the trans-
formation of functional groups and/or site-directed introduc-
tion of additional functions in the imprinted cavities, such as
on/off switching, signaling, catalytic functions, and other
desirable features.
Herein, we propose a strategy for fabricating antibody-
relevant MIPs, followed by newly designed PIMs in which
multiple programmable functional groups are independently
introduced only within the molecular recognition nanocavity.
This PIM step provides MIPs with functions capable of
differentiating from natural proteins. Herein, we demonstrate
fluorescent signaling antibody-like MIPs for a-fetoprotein
[
*] R. Horikawa, Dr. H. Sunayama, Dr. Y. Kitayama, Dr. E. Takano,
Prof. Dr. T. Takeuchi
Graduate School of Engineering, Kobe University
1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501 (Japan)
E-mail: takeuchi@gold.kobe-u.ac.jp
Dr. H. Sunayama
Current address: Department of Pharmacy
Yasuda Women’s University (Japan)
(AFP), a biomarker to detect hepatocellular carcinoma and
other cancers of the liver. Our strategy is to use covalent-type
protein-imprinting involving the formation of the template
molecule comprising AFP covalently coupled with two
different cleavable functional monomers. Subsequently,
Supporting information and the ORCID identification number(s) for
Angew. Chem. Int. Ed. 2016, 55, 1 – 6
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!