Conformational study of the cyclo(L-Trp-L-Trp)dipeptide

 

J. Hudecová1,2, J. Horníček2,3, M. Buděšínský2, J. Šebestík2 and P. Bouř2

 

1 Institute of Physics, Faculty of Mathematics and Physics, Charles University,  Ke Karlovu 5, 121 16 Prague 2

2 Institute of Organic Chemistry and Biochemistry, Academy of Sciences, Flemingovo nám. 2,             166 10 Prague 6

3 Department of Natural Compounds,  Institute of Chemical Technology, Technická  5, 166 28 Prague 6

 hudecova@uochb.cas.cz

 

 

Cyclic dipeptides are convenient model compounds because they have a restricted flexibility due to the ring containing two peptide bonds [1]. Some cyclic peptides are also known to possess antiviral, antibiotic, and anti-tumour activity.

The aim of our study is to understand the interaction of two aromatic tryptophan sidechains in c(Trp-Trp) on the basis of DFT calculations and experimental vibrational spectra. Previous studies suggest that the diketopiperazine ring is nonplanar [2],[3]. This was studied for two simplified models, cyclo(Gly-Gly) and cyclo(L-ala-L-Ala), the potential energy surface has been calculated in Gaussian 09 (B3LYP/6-311++G**, DMSO solvent). Two shallow minima have been found. For cyclo(L-Trp-L-Trp), equilibrium conformations were found also for the sidechains. Geometries with the lowest energies were used for calculation of Raman and ROA spectra.  

Raman spectra of different conformations were similar, whereas Raman optical activity (ROA, the difference in scattering for right and left circularly polarized light) spectra were more sensitive to structural details, and could better distinguish positions of the tryptophane residues and nonplanarity of the central ring.

1.  C. Prasad, Peptides 16 (1995), 151.

2.  A. P. Mendham, T. J. Dines, M. J. Snowden, B. Z. Chowdhry, and R. Withnall, J. Raman Spectrosc. 40 (2009),

     1478.

3.  Bouř, P.; Sychrovský, V.; Maloň, P.; Hanzlíková, J.; Baumruk, V.; Pospíšek, J; Buděšínský, M. J. Phys. Chem. A

     106 (2002), 7321-7327.

 

Support from the Grant Agency of the Charles University (project 126310), KONTAKT II MSMT program (LH11033), Grant Agency of the Czech Republic (P208/11/0105) and Academy of Sciences (M200550902) is gratefully acknowledged.