Conformationspecific infrared spectroscopy of gasphase protonated helical peptides

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Conformation-specific infrared spectroscopy of gas-phase protonated helical peptides Jaime A. Stearns, Monia Guidi, Ulrich

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 9/29/2020

Goal: to characterize the conformations and energy landscape of biological molecules • Characterize a

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

Experimental setup 22 -pole ion trap (6 K) S 1 fragments UV S 0

Experimental setup 22 -pole ion trap (6 K) S 1 fragments UV S 0

Infrared-ultraviolet double resonance spectroscopy B A S 1 detected fragments fragmentation threshold UV UV

Infrared-ultraviolet double resonance spectroscopy B A S 1 detected fragments fragmentation threshold UV UV only UV+IR v=1 IR S 0 IR Wavenumber /cm-1

Detailed characterization of a small helix Ac-Phe-(Ala)5 -Lys-H+ (% of ideal helix) C 13

Detailed characterization of a small helix Ac-Phe-(Ala)5 -Lys-H+ (% of ideal helix) C 13 C 10 B A Hudgins, R. R. and M. F. Jarrold (1999). JACS 121: 3494 -3501. D C

Ac-Phe-(Ala)5 -Lys-H+ IR spectra A B C D

Ac-Phe-(Ala)5 -Lys-H+ IR spectra A B C D

Low-energy conformations of Ac-Phe-(Ala)5 -Lys-H+ B gauche – (0 k. J/mol) B 3 LYP/6

Low-energy conformations of Ac-Phe-(Ala)5 -Lys-H+ B gauche – (0 k. J/mol) B 3 LYP/6 -31 G** zero-point corrected A gauche + (4 k. J/mol) D C gauche – (3 k. J/mol) gauche + (7 k. J/mol)

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

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

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

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

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

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

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

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

Fragmentation of larger molecules Ac-Phe-(Ala)7 -Lys(H+)-(Pro)2 -(Ala)5 -Lys-H+ O. V. Boyarkin et al. Far.

Fragmentation of larger molecules Ac-Phe-(Ala)7 -Lys(H+)-(Pro)2 -(Ala)5 -Lys-H+ O. V. Boyarkin et al. Far. Disc. 102: 167 -178 (1995) O. V. Boyarkin et al. J. Chem. Phys. 107: 8410 -8422 (1997)

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

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

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

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

Conclusions Small Helices • Ac-Phe-(Ala)5 -Lys-H+exists in four conformations, with two helix structures and

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

Acknowledgements Prof. Tom Rizzo Dr. Annette Svendsen Dr. Catherine Servis, Protein and Peptide Chemistry

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