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"High resolution structures of biomaterials"

Rotational spectroscopy provides the highest resolution structures of amino acids and peptides – the building blocks of life.[1-7] Molecular moments of inertia, derived from spectra fitting, are used to determine conformational structures, and atomic coordinates can be determined to within a picometer or less. The high sensitivity of Fourier-transform microwave spectrometers has allowed us to investigate large amino acid derivatives and small peptides.[8-12] We are now implementing a laser-desorption source to vaporize still larger polypeptides. Large polypeptides that form a-helix or ß-sheet structures are currently beyond the reach of rotational spectroscopists, but the recent ion-drift experiments [13-15] on acetyl-(alanine)7-lysine suggest that the first direct observations of the structural motifs found in protein and peptide secondary structure using high resolution spectroscopy may not be far off. Undergraduate students in our research group, including summer REU participants, are working towards that goal. Twelve undergraduate students have worked in the Tubergen laboratory and have contributed to eight publications in the past eight years [8,9,10, 16-20]. Summer research in such a physical chemistry research group provides a very diverse set of practical experiences for an undergraduate student. For example, a number of undergraduates have successfully synthesized isotopically labeled (15N, 2H, 13C) amino acid derivatives and peptides. The isotope synthesis projects provide practical experience in peptide synthesis, purification, and analysis of intermediates using NMR, IR, and MS. Other students have tackled the rotational spectroscopy of these species. Undergraduates have learned to operate the Fourier-transform microwave spectrometer, assign spectra, and perform ab-initio calculations using Gaussian.

1. Brown, R. D.,Godfrey, P. D., Storey, J. W. V., Bassez, M. - P., Microwave Spectrum and Conformation of Glycine, J. Chem. Soc., Chem. Commun. 547 – 548 (1978).
2. Suenram, R. D., Lovas, F. J., Millimeter Wave Spectrum of Glycine, J. Mol. Spectrosc. 72, 372 – 382 (1978).
3. Suenram, R. D., Lovas, F. J., Millimeter Wave Spectrum of Glycine. A New Conformer, J. Am. Chem. Soc., 102, 7180 – 7184 (1980).
4. Godfrey, P. D., Brown, R. D., Shape of Glycine, J. Am. Chem. Soc. 117, 2019 – 2023 (1995).
5. Lovas, F. J., Kawashima, Y., Grabow, J.-U., Suenram, R. D., Fraser, G. T., Hirota, E., Microwave Spectra, Hyperfine Structure, and Electric Dipole Moments for Conformers I and II of Glycine, Astrophys. J. 455, L201 - L204 (1995).
6. McGlone, S. J., Elmes, P. S., Brown, R. D., Godfrey, P. D., Molecular Structure of a Conformer of Glycine by Microwave Spectroscopy, J. Mol. Struct. 485-486, 225 – 238 (1999).
7. Godfrey, P. D., Firth, S., Hatherley, L. D., Brown, R. D., Pierlot, A. P., Millimeter-Wave Spectroscopy of Biomolecules: Alanine, J. Am. Chem. Soc. 115, 9687 – 9691 (1993).
8. Kuhls, K. A., Centrone, C. A*., Tubergen, M. J., Microwave Spectroscopy of the Twist Cß-Exo/CG-Endo Conformation of Prolinamide, J. Am. Chem. Soc. 120, 10194 – 10198 (1998).
9. Lavrich, R. J., Farrar, J. O*., Tubergen, M. J., Heavy-Atom Structure of Alaninamide from Rotational Spectroscopy, J. Phys. Chem. A 103, 4659 – 4663 (1999).
10. Lavrich, R. J., Tubergen, M. J., Conformation and Hydrogen Bonding in the Alaninamide-Water van der Waals Complex, J. Am. Chem. Soc. 122, 2938 – 2943 (2000).
11. Lavrich, R. J., Torok, C. R*., Tubergen, M. J., Effect of the Bulky Side Chain on the Backbone Structure of the Amino Acid Derivative Valinamide, J. Phys. Chem. A 106, 8013 – 8018 (2002).
12. Lavrich, R. J., Plusquellic, D. F., Suenram, R. D., Fraser, G. T., Hight Walker, A. R., Tubergen, M. J., Experimental Studies of Peptide Bonds: Identification of the C7eq Conformation of the Alanine Dipeptide Analogue N-Acetyl-Alanine N-Methylamide from Torsion-Rotation Interactions, J. Chem. Phys 118, 1253 – 1265 (2003).
13. Dugourd, P., Hudgins, R. R., Clemmer, D. E., Jarrold, M. F., High Resolution Ion Mobility Measurements, Rev. Sci. Instrum. 68, 1122 – 1129 (1997).
14. Hudgins, R. R., Ratner, M. A., Jarrold, M. F., Design of Helices That Are Stable in Vacuo,, J. Am. Chem. Soc. 120, 12974 – 12975 (1998).
15. Kinnear, B. S., Hartings, M. R., Jarrold, M. F., The Energy Landscape of Unsolvated Peptides: Helix Formation and Cold Denaturation in Ac-A4G7A4+H+, J. Am. Chem. Soc. 124, 4422 – 4431 (2002).
16. *Torok, C. R., Lavrich, R. J., Tubergen, M. J., Spectroscopic and ab initio Structure of the Heterocyclic Ring Tetrahydrothiophen-3-one, J. Mol. Struct. 612, 223 – 230 (2002).
17. Lavrich, R. J., *Rhea, R. L., McCargar, J. W., Tubergen, M. J., Rotational Spectroscopy and Ring-Puckering Conformation of 3-Hydroxytetrahydrofuran, J. Mol. Spectrosc. 199, 138 – 143 (2000).
18. Lavrich, R. J., *Farrar, J. O., Tubergen, M. J., Heavy-Atom Structure of Alaninamide from Rotational Spectroscopy, J. Phys. Chem. A 103, 4659 – 4663 (1999).
19. Kuhls, K. A., *Centrone, C. A., Tubergen, M. J., Microwave Spectroscopy of the Twist C?-Exo/C?-Endo Conformation of Prolinamide, J. Am. Chem. Soc. 120, 10194 – 10198 (1998).
20. Tubergen, M. J., *Flad, J. E., Del Bene, J. E., Microwave Spectroscopic and ab initio Studies of the Hydrogen-Bonded Trimethylamine-Hydrogen Sulfide Complex, J. Chem. Phys. 107, 2227 – 2231 (1997).