Disulfide bonds are important structural
motifs in natural and engineered peptides and
proteins.
Synthetic
Strategies
Usually a peptide containing disulfide bonds is first assembled in a linear form with
Cys in its sequence via either solution phase or solid phase
synthesis, then followed by the oxidation of the thiol groups to
form disulfide bonds. If there is only one pair of Cys, the
formation of disulfide bond is pretty straight
forward. If there are more than one pair of Cys, the
formation of disulfide bonds becomes complicated. All the Cys may
oxidized to form thermodynamically stable
products by scrambling with a suitable oxidative reagent in one batch process. Another
approach is to form one pair of Cys selectively at a time
while other Cys are still protected. Concentration,
pH, and solubility are among the most important factors to
get good results.
Oxidative
Reagents
Many oxidative reagents, such as oxygen (air), dimethyl sulphoxide,
oxidized glutathione, potassium ferricyanide, thallium(III)
trifluro aectate, have been used to accomplish such a
thiol-disulfide conversion. Recently, an efficient
reagent, trans-[Pt(en)2Cl2]2+,
has been reported for the quantitative formation of
intra-molecular disulfide bonds in peptides [J. Am. Chem.
Soc., (2001), 122, 6809-6815].
Examples
Princeton BioMolecules has developed different methodologies for the
formation of disulfide bonds in different peptides.
Recently we have produced a series of disulfide containing
peptides in high yields. Following are some examples.
1.
[H]- ABCDEF-X-GHIJKLMNO-X-PQRST
-[OH]
Where
X represents Cys [NOTE:
Amino acids are presented by ABCDEF.... to preserve the
confidentiality]. A
disulfide bond is formed between the two Xs.
The amino acids at various positions may be replaced by
either D-form or special amino acids. Totally 25
peptides were made in this series.
2.
[H]- X-GHIJKLMNO-X
-[OH]
Where
X is at the end of sequence. Totally 10 peptides were made in this
series.
3.
[H]- A-X-LMNO-X-B
-[OH]
Where
the two Xs is only four amino acids apart.
Totally 8 peptides were made in this series.
The
oxidation is monitored by Ellman Test for the amount of
thiol group left and by rp-HPLC for the progress of
transformation. The final products are purified by
rp-HPLC and verified by HPLC and mass spectrum.
Princeton BioMolecules offer the best service of custom
synthesis of peptides containing disulfide bonds. If
you involve in any research requiring disulfide peptides in
peptides, please feel
free to contact us.
Back
to Home Page
