Eight analogues of DYN A(1-11)-NH2 incorporating the nonhydrolyzable Ψ[CH2-NH] peptide bond surrogate were tested for their in vitro enzymatic stability in mouse brain homogenates. Results show that the Leu5-Arg6 and to a lesser extent the Arg7-Ile8 and Ile8-Arg9 peptide bonds are the more susceptible to enzymatic cleavage in the native peptide. (Leu5Ψ[CH2-NH]Arg6)DYN A(1-11)-NH2 exhibits an almost complete resistance to enzymatic cleavage with a half-life greater than 500 min in brain, compared to 42 min for the standard peptide, DYN A(1-11)-NH2.
- Dynorphin A
- Enzymatic stability
- Ψ[CH-NH] reduced bond
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience