The design, solid-phase synthesis, and photochemical validation of diverse peptide linchpins, containing the S,S-tetrazine
phototrigger, have been achieved. Steady state irradiation or
femtosecond laser pulses confirm their rapid photofragmentation.
Attachment of peptides to the C- and N-termini will
provide access to diverse constrained peptide constructs that hold the
promise of providing information about early peptide/protein
conformational dynamics upon photochemical release.
The S,S-tetrazine scaffold possesses a number of advantages when
compared to other nonreversible trigger systems: (1) flash photolysis
can be conducted with near-UV (λ=355 or 410 nm) laser pulses, which
would not lead to damage of the peptide; (2) acceptable photolysis
yields are observed; and (3) the thiocyanate photoproducts are
relatively inert and provide a potentially useful IR probe.