1. Conformation-specific infrared spectroscopy of gas-phase protonated helical peptides
Jaime A. Stearns, Monia Guidi, Ulrich Lorenz,
Caroline Seaiby, Oleg V. Boyarkin and Thomas R. Rizzo
Laboratoire de Chimie Physique Moléculaire
Ecole Polytechnique Fédérale de Lausanne
5 December 2018

2. Goal: to characterize the conformations and energy landscape of biological molecules
Characterize a small helix in detail
Understand the influence of the chromophore on conformation
Characterize a segmented helix with one chromophore
*** fragmentation of large molecules

3. Experimental setup
22-pole ion trap
(6 K) S1
fragments UV S0

4. Infrared-ultraviolet double resonance spectroscopy
detected
fragments
fragmentation
threshold UV
UV only
v=1
UV+IR IR S0
IR Wavenumber /cm-1

5. Detailed characterization of a small helix
Ac-Phe-(Ala)5-Lys-H+
C13
(% of ideal helix)
C10 B D A C
Hudgins, R. R. and M. F. Jarrold (1999). JACS 121:

6. Ac-Phe-(Ala)5-Lys-H+ IR spectraB C D

7. Low-energy conformations of Ac-Phe-(Ala)5-Lys-H+B A
gauche –
(0 kJ/mol)
gauche +
(4 kJ/mol)
there are other degrees of freedom,
these are 4/5 lowest – 972 is the other D C
B3LYP/6-31G** zero-point corrected
gauche –
(3 kJ/mol)
gauche +
(7 kJ/mol)

8. Influence of chromophore on conformation
Ac-Phe-(Ala)5-Lys-H+
Ac-Tyr-(Ala)5-Lys-H+
Ac-Trp-(Ala)5-Lys-H+

9. Ac-Trp-(Ala)5-Lys-H+
Ac-Phe-(Ala)5-Lys-H+ Conformer C

10. Ac-Tyr-(Ala)5-Lys-H+ B A

11. A B Ac-Tyr-(Ala)5-Lys-H+ Ac-Phe-(Ala)5-Lys-H+ Conformer C
Ac-Phe-(Ala)5-Lys-H+ Conformer A

12. Fragmentation of larger molecules
Ac-Phe-(Ala)7-Lys(H+)-(Pro)2-(Ala)5-Lys-H+
O.V. Boyarkin et al. Far. Disc. 102: (1995)
O.V. Boyarkin et al. J. Chem. Phys. 107: (1997)

13. Segmented Helix: Ac-Phe-(Ala)7-Lys(H+)-(Pro)2-(Ala)5-Lys-H+B C

14. Segmented Helix: Ac-Phe-(Ala)7-Lys(H+)-(Pro)2-(Ala)5-Lys-H+B C

15. Ac-Phe-(Ala)7-Lys(H+)-(Pro)2-(Ala)5-Lys-H+
Conclusions
Small Helices
Ac-Phe-(Ala)5-Lys-H+exists in four conformations, with two helix structures and two phenyl ring orientations
Ac-Tyr-(Ala)5-Lys-H+ and Ac-Trp-(Ala)5-Lys-H+ have similar but fewer conformations
Ac-Phe-(Ala)7-Lys(H+)-(Pro)2-(Ala)5-Lys-H+
Demonstrates power of IRLAPS
Shows resolved IR and UV spectra
The Next Steps
Conformational assignments of segmented helix
Segmented helix with multiple chromophores

16. Protein and Peptide Chemistry Facility
Acknowledgements
Prof. Tom Rizzo
Dr. Oleg Boyarkin
Monia Guidi
Caroline Seaiby
Dr. Annette Svendsen
Ulrich Lorenz
George Papadopoulos
Natalia Nagornova
Dr. Catherine Servis,
Protein and Peptide Chemistry Facility
Funding: Swiss NSF, EPFL