Peptide-Based Drug Design

Peptidomimetics 225
O O
R
S
N
H
Peptidosulfonamides
ψ[CH2-SO2-NH] O
P
O
R OH
R 1
Phosphonopeptides
ψ[P(=O)OH-O]
O R
N N
H H
Oligoureas
ψ[CH2-NH-CO-NH] O R
N
H
Peptides
O R
C
O
Depsides and
depsipeptides
ψ[C(=O)-O]
O
C
N
R
Peptoids
ψ[C(=O)-N(R)CH2 ]
Fig. 1. Schematic representation of peptidomimetics containing the amide surrogates
that are isosteric with the natural peptidic amide bonds.
2. Materials
1. All materials and reagents are commercially available and used as received.
2. Synthesis solvents, such as dichloromethane (DCM), dimethoxyethane (DME),
acetic acid (AcOH), ethyl acetate (EtOAc), tert-butanol (t-BuOH), 1-methyl-
2-pyrrolidinone (NMP), tetrahydrofurane (THF), methanol (MeOH), toluene,
benzene, N,N´-dimethylformamide (DMF), methyltertbutylether (MTBE),
hexane, dimethylsulfoxide (DMSO), and diethyl ether, were synthesis or peptide
synthesis grade (if necessary) and can be obtained from Sigma-Aldrich, Fisher,
VWR, or other commercial sources.
3. Peptide synthesis reagents such as diisopropylcarbodiimide (DIC), benzotriazole-
1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBOP), bromotris-pyrrolidino-phosphonium
hexafluorophosphate (PyBroP), 2-(1Hbenzotriazole-1-yl)-1,1,3,3-tetramethyluronium
hexafluorophosphate (HBTU),
1-hydroxybenzotriazole (HOBt), piperidine, N-methylmorpholine (NMM),
trifluoroacetic acid (TFA), triisopropylsilane (TIS), N,N-diisopropylethylamine
(DIPEA, DIEA), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,2-ethanedithiol
(EDT), and 4-dimethylaminopyridine (DMAP) may be obtained from Sigma-
Aldrich, ChemImpex, and Novabiochem.