Eight analogues of DYN A(1-11)-NH2 incorporating the nonhydrolyzable p
si[CH2-NH] peptide bond surrogate were tested for their in vitro enzym
atic stability in mouse brain homogenates. Results show that the Leu(5
)-Arg(6) and to a lesser extent the Arg(7)-Ile(8) and Ile(8)-Arg(9) pe
ptide bonds are the more susceptible to enzymatic cleavage in the nati
ve peptide. (Leu5 psi[CH2-NH]Arg(6))DYN A(1-11)-NH2 exhibits an almost
complete resistance to enzymatic cleavage with a half-life greater th
an 500 min in brain, compared to 42 min for the standard peptide, DYN
A(1-11)-NH2.