In vitro stability of some reduced peptide bond pseudopeptide analogues of dynorphin A.
Eight analogues of DYN A(1-11)-NH2 incorporating the nonhydrolyzable psi [CH2-NH] peptide bond surrogate were tested for their in vitro enzymatic stability in mouse brain homogenates. Results show that the Leu(5)-Arg6 and to a lesser extent the Arg(7)-Ile8 and Ile(8)-Arg9 peptide bonds are the more susceptible to enzymatic cleavage in the native peptide. (Leu5 psi[CH(2)-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.
Department of Chemistry, University of Arizona, Tucson 85721, USA.
J P
JP
Meyer
T J
TJ
Gillespie
S
S
Hom
V J
VJ
Hruby
T P
TP
Davis
D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D004355:Drug Stability; D004399:Dynorphins / Q000737:chemistry* / Q000493:pharmacokinetics*; D010450:Endopeptidases / Q000378:metabolism*; D006207:Half-Life; D008297:Male; D051379:Mice
D004399:Dynorphins; D010450:Endopeptidases