30
2 Synthesis of In-Tether Chiral Center Peptides …
Scheme 2.3 The
representative synthesis
procedures for pentapeptides
(MAP:
4-methoxyacetophenone,
hydroxyethoxy)-2methylpropiophenone,
DIEA: N,
N-diisopropylethylamine),
TIS: Triisopropylsilane
FmocHN
NH
O
R
(1) HCTU,DIEA,AAs
(2) Acetic anhydride, DIEA
Rink amide MBHA resin
95%TFA:2.5%H 2 O:2.5%TIS
H
N
N
H
H
N
N
H
O
O
O
NH 2
O
O
N
H
S
O
R
H
N
N
H
H
N
N
H
O
O
O
NH
O
O
N
H
STrt
O
MAP,MMP
H
N
N
H
H
N
N
H
O
O
O
NH
O
O
N
H
S
O
TFA:TIS:DCM
=5:3:92
R
R
H
N
N
H
H
N
N
H
O
O
O
NH
O
O
N
H
SH
O
R
365nm
reverse-phase HPLC, suggesting significant conformational differences in solution.
All peptides categorized in group b have longer retention times when compared to
their diastereomers in group a. Circular dichroism (CD) spectroscopy measurements
clearly show that peptide 1a is a random coil while 1b is helical in PBS buffer (PH
= 7.0, Fig. 2B).
A series of single turn peptides with varying sequences were tested and all peptide
diastereomers (peptides 2a/2b to peptides 10a/10b) were easily separable by HPLC.