Characterization of Ultraviolet Photoreactions in Therapeutic Peptides by Femtosecond Laser Catalysis and Mass Spectrometry

Simon K Gammelgaard, Steffen B Petersen, Kim F Haselmann, Peter Kresten Nielsen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Peptides and proteins have diverse ultraviolet (UV) photoreaction pathways that can be activated by the energy of the UV photons absorbed. Simple light sources such as lamps are conventionally used to study these photoreactions in solution. This work provides a proof of concept that femtosecond laser technology can function as a highly potent UV source in rapidly conducting UV photostability studies of peptides. Correspondingly, sufficient quantities of photoproducts were generated in 1 min or less, allowing for identification of known and new photomodifications in the therapeutic peptides somatostatin-14 and arginine vasopressin. Identical photoproducts were also generated with a conventional continuous source. The major modifications included N-formylkynurenine, a cross-link between Trp and Phe, a Tyr product with an NH3 loss, and disruption of an unstable disulfide bond into a complex mixture of a trisulfide bond and multiple scrambled dimeric products. In conclusion, femtosecond lasers are extremely useful to drive fast UV-induced reactions for high throughput screening of photostability and modifications in amino acid polymers.

OriginalsprogEngelsk
TidsskriftACS Omega
Vol/bind4
Udgave nummer11
Sider (fra-til)14517-14525
Antal sider9
DOI
StatusUdgivet - 10 sep. 2019

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Ultrashort pulses
Peptides
Catalysis
Mass spectrometry
Arginine
Arginine Vasopressin
Somatostatin
Complex Mixtures
Electric lamps
Disulfides
Light sources
Amino acids
Screening
Polymers
Photons
Throughput
Proteins
Amino Acids

Citer dette

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abstract = "Peptides and proteins have diverse ultraviolet (UV) photoreaction pathways that can be activated by the energy of the UV photons absorbed. Simple light sources such as lamps are conventionally used to study these photoreactions in solution. This work provides a proof of concept that femtosecond laser technology can function as a highly potent UV source in rapidly conducting UV photostability studies of peptides. Correspondingly, sufficient quantities of photoproducts were generated in 1 min or less, allowing for identification of known and new photomodifications in the therapeutic peptides somatostatin-14 and arginine vasopressin. Identical photoproducts were also generated with a conventional continuous source. The major modifications included N-formylkynurenine, a cross-link between Trp and Phe, a Tyr product with an NH3 loss, and disruption of an unstable disulfide bond into a complex mixture of a trisulfide bond and multiple scrambled dimeric products. In conclusion, femtosecond lasers are extremely useful to drive fast UV-induced reactions for high throughput screening of photostability and modifications in amino acid polymers.",
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Characterization of Ultraviolet Photoreactions in Therapeutic Peptides by Femtosecond Laser Catalysis and Mass Spectrometry. / Gammelgaard, Simon K; Petersen, Steffen B; Haselmann, Kim F; Nielsen, Peter Kresten.

I: ACS Omega, Bind 4, Nr. 11, 10.09.2019, s. 14517-14525.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Characterization of Ultraviolet Photoreactions in Therapeutic Peptides by Femtosecond Laser Catalysis and Mass Spectrometry

AU - Gammelgaard, Simon K

AU - Petersen, Steffen B

AU - Haselmann, Kim F

AU - Nielsen, Peter Kresten

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