4th EucheMs chemistry congress

tuesday, 28-Aug 2012
s711
chem. Listy 106, s587–s1425 (2012)
life sciences
life science Multisymposium – ii
o - 1 9 2
SyntheSiS, ProPertieS, And APPLiCAtionS of
CovALentLy tethered MiniCoLLAGenS
f. weiher 1 , A. Geyer 1
1 Philipps University Marburg, Organic Chemistry, Marburg,
Germany
C-terminal capping of three collagen peptides yields
synthetic minicollagens of scalable lengths and melting
temperatures. The covalently tethered triple helix is a
non-bendable rod whose thermodynamic stability significantly
differs from a monomeric PUG strand. Minicollagens adopt triple
helical conformations independent of pH and buffers and
therefore can serve as building blocks for molecular bionic
designs. Their spectroscopic properties and an example of a
[1, 2]
possible application in material science are presented here.
Chiral triamines can fit the required stagger of the triple
helix. These capping groups contribute to triple helix stabilization
by ensuring an in-phase start of the triple helix. The cap optimized
in length and chirality is improving the melting temperature by
more than 20 °C. In this presentation we show that trimeric
architectures of minicollagens up to sizes of almost 90 amino
acids can be synthesized within one day in good qualities. [3]
Higher melting temperatures increase the range for
minicollagens of certain lengths to exhibit a sigmoid melting
behaviour. Physicochemical analyses also state a fast folding of
those collagen derivatives. Contrasting previously synthesized
collagens, the molecules presented here exhibit triple helical
folding without incubation times. This opens new application
fields for the minicollagens. One example from Material Science
will be presented. [4]
references:
1. A. Persikov, J. Ramshaw, A. Kirkpatrick, B. Brodsky,
J. Am. Chem. Soc. 2003, 125, 11500.
2. M. D. Shoulders, R. T. Raines, Annu. Rev. Biochem 2009,
78, 929.
3. F. Weiher, A. Geyer, manuscript in preparation.
4. F. Weiher, M. Schatz, C. Steinem, A. Geyer, manuscript in
preparation.
Keywords: Peptides; Collagen; Sold-Phase Peptide-Synthesis;
life science Multisymposium – ii
4 th EucheMs chemistry congress
o - 1 9 3
dnA reCoGnition: new SPeCifiC AGentS And
fLuoreSCent ProBeS
o. vázquez 1 , M. i. SánChez 1 , M. e. vázquez 1 ,
J. L. MASCArenAS 1
1 Centro Singular de Investigación en Química Biológica y
Materiales Moleculares, Departamento de química orgánica,
Santiago de Compostela (A Coru, Spain
Deciphering the human genome has opened new
perspectives in biomedical research, promising improved
diagnostic techniques and personalized therapies. However, to
fully exploit the knowledge about our genes, it is necessary to
develop probes capable of targeting and sensing specific DNA
sequences. In the recent decades there have been significant
contributions in the area of dsDNA recognition. However, despite
the enormous developments in this area, specific targeting of
particular DNA sequences still remains an unsolved problem in
chemical biology.
In this context, during the last decade our group has reported
some successful discoveries in the design, synthesis and study of
non-natural peptide derivatives, which despite being structurally
simpler, are capable of mimicking the DNA binding properties of
the transcription factors. [1] Here, we present our steps forward in
this field.
a) Development of specific DNA recognition by synthetic,
monomeric Cys His Zinc finger peptide conjugated to a
2 2
minor groove binder. [2]
b) Discovery of the fluorogenic properties of the DNA
minor groove binder BAPPA and applications. [3]
c) Straightforward access to bisbenzamidine DNA binders
and use as versatile adaptors for DNA-promoted process. [4]
references:
1. a) Vázquez, M. E.; Caamano, A. M. Martínez-Costas, J;
Castedo, L.; Mascarenas, J. L., Angew. Chem. Int. Ed.
2001, 40, 4723–4725;
b) Blanco, J. B.; Vázquez, M. E.; Castedo, L.; Mascarenas,
J. L., ChemBioChem 2005, 6, 2173–2177.
2. Vázquez O.; Vázquez, M. E.; Blanco, J. B.; Castedo, L.
Mascarenas, J. L., Angew. Chem. Int. Ed. 2007, 46,
6886–6890;
3. a) Vázquez, O.; Sánchez, M. I.; Martínez-Costas, J.;
Vázquez, M. E.; Mascarenas, J. L. Org. Lett. 2010, 12,
216–219.
b) Vázquez, O.; Sánchez, M. I.; Mascarenas, J. L.;
Vázquez, E. M. Chem. Commun. 2010,14, 5518–20.
4. Sánchez, M. I.; Vázquez, O.; Martínez-Costas, J.;
Vázquez, M. E.; Mascarenas J. L. Chem. Sci in press
DOI:10.1039 / C2SC00027J.
Keywords: Molecular recognition; DNA; Fluorescence;
Peptides; Transcription factors;
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc