Back to Table of Contents

40642-AC6
Spectroscopy of Individual Small Model Peptides and Their Clusters with Water

Mattanjah S. De Vries, University of California (Santa Barbara)

Understanding the details of molecular shapes is fundamental to understanding many aspects of their chemical function. We have therefore undertaken to study the conformational landscapes of small poly-aminoacids. We have used IR-UV double resonant spectroscopy of laser-desorbed and jet-cooled model sequences to determine folding patterns. We have analyzed the xperimental spectra with high level quantum computations.

1. Model study of FGG.

This molecule serves as a model system. It is the smallest possible tripeptide with a chromophore. We have therefore studied it in great detail, experimentally as well as computationally, the latter in collaboration with Prof. Hobza in Prague. We developed and formulated a strategy for complete structural analysis of these types of molecules, which we can follow in subsequent work. We also performed experiments on the same model tripeptide in the mid IR at the FELIX free electron laser facility in the Netherlands.

2. Charge transfer in FGG

We have studied photodissociation of FGG ions as a function of their initial conformation. Our technique and previous analysis now allow us to select a specific molecular shape from which we form the ion. We found the dissociation dynamics to depend strongly on the starting conformation and propose a model of shape dependent charge transfer to interpret the results.

3. Folding in YGG.

This tripeptide constitutes the next step with the addition of an OH group. We performed a systematic a study of the sequence Y, YG, YGG and found evidence for the onset of peptide folding upon addition of the third amino acid.

4. Excited state dynamics in GFA

In GFA an entire family of low energy conformations predicted by the calculations is missing in the experimental results. These structures all involve a specific hydrogen bond. Our interpretation is that the cause is an excited state with a sub-picosecond lifetime, which eludes our nanosecond timescale detection. This is a phenomenon which we also observe in our studies of nucleobases. This effect of excited state dynamics is likely to play an important role in the protection of biomolecules against UV radiation damage.

5. Chirality

We studied the hetero-dipeptides LL-VF (L-Val-L-Phe) and DL-VF and the homo-dipeptides LL-FF (L-Phe-L-Phe) and LD-FF. Changing one of the chiral centers in each molecule, leads to changes in the spectra that can be used to distinguish between diastereoisomeric pairs.

6. Cyclic peptides

We studied the cyclic dipeptide Phe-Ser. We found surprisingly that the cyclization of the Phe-Ser, does not change the number of low energy conformers that are frozen in the beam compared to the linear form of this peptide. However, the rigidity of the cyclic peptide is evident in the vibrational spectra. We found that the R group of the serine residue is playing an important rule in shaping the structure of each conformer by intramolecular hydrogen bonding involving its hydroxyl group.

7. Enkaphelins.

As a stepping stone to the study of enkaphelins, a pentapeptide, we first studied the isomeric tetrapetide sequences FGGF and FGFG. Subsequently we obtained detailed data on meta-enkaphelin in the near IR. We collaborate with the group of Dr. Snoek in Oxford, who obtained complimentary data in the mid IR at FELIX. This is the first example of the complete characterization of an isolated peptide over the entire IR range. A number of theoretical groups are performing high level quantum calculations for which they can use our data as a benchmark.

8. FDASV

The smallest peptide that can form an α turn motif requires 5 residues. IR-UV double resonance spectroscopy of the laser-desorbed, jet-cooled pentapeptide FDASV shows only one type of conformer in the gas phase. Comparison with computations at the B3LYP/6-31G** level suggests formation of an α turn in the absence of solvent stabilization. This structure is stabilized by internal hydrogen bonding. This is the first observation of an α turn in the gas phase.

9. Larger peptides.

We reported on the first double resonant IR-UV spectroscopy of isolated gramicidins, a set of 15 residue peptides. This result shows not only that it is possible to bring these larger peptides into the gas phase intact, but also that in this way high resolution spectroscopy can be performed on them, in spite of the large number of internal degrees of freedom. Furthermore these peptides appear to maintain their secondary structure in the gas phase.

This work has resulted in 9 publications. Five have been published already while four more have been submitted or will be submitted in the near future.

Back to top