Presentation Title

Facile removal of 4‐methoxybenzyl protecting group from selenocysteine

Project Collaborators

Gracyn Mose (Undergraduate Collaborator)

Abstract

Historically, methods to remove the 4‐methoxybenzyl (Mob)–protecting group from selenocysteine (Sec) in peptides have used harsh and toxic reagents. The use of 2,2′‐dithiobis‐5‐nitropyridine (DTNP) is an improvement over these methods; however, many wash steps are required to remove the by‐product contaminant 5‐nitro‐2‐thiopyridine. Even with many washes, excess DTNP adheres to the peptide. The final product needs excess purification to remove these contaminants. It was recently discovered by our group that hindered hydrosilanes could be used to reduce Cys(Mob). We sought to apply a similar methodology to reduce Sec(Mob), which we expected to be even more labile. Here, we present a gentle and facile method for deprotection of Sec(Mob) using triethylsilane (TES), phenol, and a variety of other scavengers often used in deprotection cocktails. The different cocktails were all incu- bated at 40 °C for 4 hours. The combination of TFA/TES/thioanisole (96:2:2) appeared to be the most efficient of the cocktails tested, providing complete deprotection and yielded peptide that was mainly in the diselenide form. This cocktail also showed no evidence of side reactions or significant contaminants in the high‐performance liquid chromatography (HPLC) and mass spectral (MS) analyses. We envision that our new method will allow for a simple and gentle “one‐pot” deprotection of Sec(Mob) following solid‐phase peptide synthesis and will minimize the need for extensive purification steps.

Primary Faculty Mentor Name

Robert Hondal

Secondary Mentor NetID

ERuggles

Secondary Mentor Name

Erik Ruggles

Graduate Student Mentors

Emma Ste. Marie

Status

Undergraduate

Student College

College of Arts and Sciences

Program/Major

Chemistry

Primary Research Category

Engineering & Physical Sciences

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Facile removal of 4‐methoxybenzyl protecting group from selenocysteine

Historically, methods to remove the 4‐methoxybenzyl (Mob)–protecting group from selenocysteine (Sec) in peptides have used harsh and toxic reagents. The use of 2,2′‐dithiobis‐5‐nitropyridine (DTNP) is an improvement over these methods; however, many wash steps are required to remove the by‐product contaminant 5‐nitro‐2‐thiopyridine. Even with many washes, excess DTNP adheres to the peptide. The final product needs excess purification to remove these contaminants. It was recently discovered by our group that hindered hydrosilanes could be used to reduce Cys(Mob). We sought to apply a similar methodology to reduce Sec(Mob), which we expected to be even more labile. Here, we present a gentle and facile method for deprotection of Sec(Mob) using triethylsilane (TES), phenol, and a variety of other scavengers often used in deprotection cocktails. The different cocktails were all incu- bated at 40 °C for 4 hours. The combination of TFA/TES/thioanisole (96:2:2) appeared to be the most efficient of the cocktails tested, providing complete deprotection and yielded peptide that was mainly in the diselenide form. This cocktail also showed no evidence of side reactions or significant contaminants in the high‐performance liquid chromatography (HPLC) and mass spectral (MS) analyses. We envision that our new method will allow for a simple and gentle “one‐pot” deprotection of Sec(Mob) following solid‐phase peptide synthesis and will minimize the need for extensive purification steps.