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Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
Chapter 8. Synthetic Receptors for Amino Acids and Peptides
Debrabata Maity and Carsten Schmuck*
University of Duisburg-Essen, Faculty of Chemistry,
Universitätsstrasse 7, 45141 Essen, Germany
*Email: [email protected]
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
Figure 8.1 Schematic of the binding of glutamate (green) in a G-protein coupled glutamate receptor with red lines
showing H-bonding and blue lines showing van der Waal contacts. (Reproduced with permission from Br. J. Clin.
Pharmacol., 2009, 156, 869, © 2009 British Pharmacological Society)
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
Figure 8.2 Model of the binding interaction between the RGD peptide (Arg-Gly-Asp) and binding site of αvβ3integrin. α- and β-Integrin subunits are represented in pink and pale cyan, respectively. The RGD residues are
shown in green, and nitrogen, oxygen atoms in blue and red, respectively. Ca(II) is represented by a red sphere.
Integrin and ligand residues involved in binding are labeled with the three- and one-letter code, respectively. Dotted
lines denote H-bonds between ligands and integrin (Reproduced with permission from J. Cell Sci., 2011, 124, 515, ©
2011 The Company of Biologists Ltd)
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
Figure 8.3 Complex structures showing: (top) vancomycin and mimic of the normal bacteria cell wall peptidyl
fragment Ac2-L-Lys-D-Ala-D-Ala, (bottom) modified vancomycin analog and mimic of the drug resistant
bacteria cell wall peptidyl fragment Ac2-L-Lys-D-Ala-D-Lac.
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
Figure 8.4 Receptors based on guanidinium groups.
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
N
N
N
OH
N
N
N
OH
2Cl
O O
O O
2Cl
OH
OH
O O
O O
N
N
N
N
N
N
2Cl
(R)-8.7
(R)-8.8
N
N
(R)-8.9
N
N
OCH 3 H 3CO
OH
HO
OCH 3 H 3CO
OH
HO
N
N
N
N
2Cl
(R)-8.10
2Cl
(R)-8.11
Figure 8.5 Receptors based on imidazolium groups.
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
CH 2
N
N
10
8.12
Figure 8.6 Receptor based on a viologen group.
(CH 2) 3CH3
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
O
OH
NH
H
HN
H
HN
S
H
S
HN
OH
NH
8.13
Figure 8.7 Receptor mainly based on hydrogen bonding.
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
O
NH
HN
NH
Cu
Cu
NH
NH
NH
R
R
N
N
H
O
N
N
Cu
Cu
R
R
H
N
O
O
8.15: R =H
8.16: R = MOM
8.14
8.17
O
O
O
O
O
N
H
N
H
NH
NH
NH
NH
O
O
O
O
O
8.18
8.19
8.20
Figure 8.8 Copper containing receptors for amino acid recognition based on indicator-displacement assays.
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
Rh
Cl
Cl
Cl
Rh
Cl
8.21
Figure 8.9 Rhodium containing receptor for amino acid recognition based on indicator-displacement assays.
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
HO
Au+
O
O
OH
N O
EtHN
O
H
NEt
Figure 8.10 Au+ containing receptor for amino acid recognition.
8.22-Au+
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
Figure 8.11 Schematic representation of the amino acid (Lys, Arg or His) induced aggregation of calix-capped gold
nanoparticles.
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
R'
R
O
H
N
O
O
O
H 3N
R
H
R'
O
O
N
N
O
O
8.23 R = H
8.24 R = Bu
Figure 8.12 Reaction of coumarin receptors with unprotected amino acids.
H
O
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
NH 2
O
H
H
OH
HO
O
N
OH
NH 2
NH 2
8.25
Figure 8.13 Recognition of Lysine by imine bond formation.
O
OH
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© The Royal Society of Chemistry 2015
Figure 8.14 Reaction based recognition of amino acids (Cys and Hcy).
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
O
N
O
R-CH 2SH
CN
N
O
CN
O
CN
CN
SCH2R
8.27
Strong Fluorescence
Weak Fluorescence
R=
CHCO 2
NH 3
Cys
CH 2 CCO 2
NH 3
Hcy
Figure 8.15 Reaction of 8.27 with sulfur-containing amino acids (Cys, Hcy, and GSH).
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
O 2N
NO 2
O
O
O
H 2N
O
S
O
OH
HS
S
NH 2
NO 2
+
8.28
N
F
B
OH
OH
N
N
F
F
B
SO2
N
F
Figure 8.16 Reaction based recognition of cysteine with 8.28.
+
NO 2
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
O
N
O
O
N
N
O
O
O
O
N
O
O
GSH
2
2
O
HN
NH
O
O
8.29
O
S
S
O
NH
+
NH 2
O
SH
Figure 8.17 Reaction of 8.29 with thiol-containing amino acids.
S
O
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
Figure 8.18 Cyclodextrin-nickel salophen complexes for recognition of L-Phe-D-Pro containing peptides in water.
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
Figure 8.19 Cyclodextrin based receptors for peptides.
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
Figure 8.20 Bis-cyclodextrin receptors used for binding dipeptides.
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
O
N
N
H
H2
C
H
N
N
C
H2
O
Q6 n = 6
Q7 n = 7
Q8 n = 8
Figure 8.21 Cucurbit[n]uril (Qn) host.
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© The Royal Society of Chemistry 2015
Figure 8.22 Macrocyclic hosts 8.42 and 8.43 which preferentially bind hydrophobic peptides in water.
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
Figure 8.23 Self-assembled coordination cage 8.44 for peptide binding in water.
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
O
COOH
R
O
H
N
N
H
O
Dye
H
N
N
H
O
COOH
H
N
O
COOH
O
R
H
N
N
H
H
O
O
N
H
N
O
COOH
O
Dye-OH =
8.45 R = Ac
8.46 R =
Dye
O
N
O 2N
HO
O
Figure 8.24 Diketopiperazine based receptors.
N
N
OH
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
NO 2
O
O
H
N
HO
H 2N
N
H
N
O
O
O
O
N
O
O
O
O
O
O
f
HN
NH
N
NH
O
HN
HO
S
HN
H 2N
NH
O
NH
O
H
N
O
O
N
H
NH 2
NH 3
N
H
S
N
O
H
N
N
NH
NH
H 2N
O
8.47
S
NH
O
N
H
O
O
H
N
O
N
H
H
N
NHAc
O
NH
8.48
Figure 8.25 Cationic guanidinium based receptors.
N
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
Figure 8.26 General structure of 2-(guanidiniocarbonyl)pyrrole functionalized receptor 8.49 and its
interaction with a tetrapeptide.
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
Figure 8.27 2-(Guanidiniocarbonyl)pyrrole modified receptor 8.50.
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
O O
P
O
H
N
O
Linker
O O
N
H
O
NH 2
N
H
NH 2
P
O
Linker =
O
H
N
N
H
O
8.51
O
O
O
H
N
N
H
8.52
H
N
O
8.53
Figure 8.28 Ditopic receptors for RGD tripeptides.
O
8.54
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
O O
O
O
O
O
O
O
N
H
O
O
N
O
O
O
O
O
O
8.55
N
NH
H
N
O
N
O
NH 2
O
8.56
HN
O
O
H
N
O
N
H
O
O
O
NH
O
N
O
NH 2
O
O
O
O
O
O
O
O
O
O
N
8.57
NH
O
O
Figure 8.29 Crown ether containing peptide receptors.
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
O
O
O
O
O
N
R
O
O
O
O
O
N
NH
NH
R=
NH
NH
N
N
H 2N
NH
8.58
H
N
N
O
8.59
Figure 8.30 Crown ether containing peptide receptors.
8.60
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
Figure 8.31 Zn complexes for recognition of phosphorylated peptide.
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
H
H
N
N
Zn2+
N
N
H
NH 2
H
N
N
HO
N
NH
O
N
H
N
N
H
NH 2
N
n
Zn2+
N
N
8.67 n = 1
8.68 n =2
H
H
H
H
H
N
H
N
Zn2+
N
N
H
N
N
N
N
H
N
H
N
H
N
N
H
OH
N
H
N
O
n
Zn2+
N
H
H
N
H
N
H
N
Zn2+
N
N
N
N
N
H
HO
N
Zn2+
N
H
8.69 n = 1
8.70 n =2
H
N
N
Zn2+
N
N
O
H
O
N
O
NH
N
HO
N
H
N
N
Zn 2+
N
H
N
Zn2+
N
OH 2
N
N
OH 2
N
O
O
O
N
H
H
O
8.71
H
H
N
N
Zn2+
N
N
O
H
N
OH 2
N
NH
N
N
Zn2+
N
H
N
N
H
O
O
N
N
HO
OH 2
N
O
O
O
Zn2+
N
N
8.72
H
H
O
O
Flu
N
H
O
H
N
N
H
O
O
O
P
O
OH
O
H
N
H
N
N
H
O
N
H
g
O
O
H
N
N
H
O
O
O
P
O
O
NH 2
O
N
Flu
O
O
H
N
N
H
O
NH
H
N
O
NH 2
O
h
Figure 8.32 Zn complexes for recognition of phosphorylated peptides.
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
O
O
O
O
R'
O
N
R
O
R'
O
O
O
O
8.73
H
N
H N
N
2+
Zn
R=
N
H
N
N
N
H
N
n
O
N
N
N
N
H
O
H
N
N
N
M 2+ N
N
+
2
Zn
m
M 2+
N
H
N
H
N
H
NHCbz
O
M 2+ = Zn2+, Mn 2+
H
N
H N
N N
N
N
2+
Zn
N
H
N
N
M 2+
N
H
N
O
Figure 8.33 Peptide receptors based on the combination of crown ether and metal complexes.
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
Figure 8.34 Histidine-coordinating Zn-nitrilotriacetic acid complex receptors.
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
Figure 8.35 Histidine-coordinating Cu-nitrilotriacetic acid complex receptors.
Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications
© The Royal Society of Chemistry 2015
N
N
N
N
N
N
Cu
N
HO
N
OH
HO
O
NH
OH 2
N
Cu
HN
N
O
R1
NH
NH
O
HN
O
R2
O
HN
O
O
HN
O
O
HN
HN
R3
O
O
NH 3
NH
HN
O
O
O
O
O
O
O
NH
O
O HN
O
NH
O
O
HN
NH
O
O
O
H 3N
O
8.78
8.79
O
N
N
N
M
L
N
L
N
N
H 2N
NH
HN
O
N
NH
R1
N
M
N
NH
NH
O
HN
HN
HN
R2
O
HN
R1
HN
O
NH
NH 3
NH 3
NH
Asp
HN
HN
O
R2
O
O
H 3N
O
NH
HN
Lys
O
O
8.80
O
R1
R3
HN
NH
O
O
R3
O
H 2N
NH 2
NH
R2
O
R3
8.81
NH 3
Figure 8.36 Metal complex receptors for peptides.