TY - JOUR
T1 - Prodrugs to enhance central nervous system effects of the TRH-like peptide pGlu-Glu-Pro-NH2
AU - Prokai-Tatrai, Katalin
AU - Nguyen, Vien
AU - Zharikova, Alevtina D.
AU - Braddy, April C.
AU - Stevens, Stanley M.
AU - Prokai, Laszlo
N1 - Funding Information:
This research has been supported by a grant from the NIH (MH59380). Laurent Marc is acknowledged for his technical assistance in the syntheses.
PY - 2003/3/24
Y1 - 2003/3/24
N2 - Potential prodrugs for the TRH-like tripeptide pGlu-Glu-Pro-NH2 were synthesized either by esterifying the Glu side-chain of the parent peptide in solution with alcohols in the presence of resin-bound dicyclohexylcarbodiimide or by solid-phase peptide chemistry. Affinities of these ester prodrugs to lipid membranes as predictors of the transport across the blood-brain barrier were compared by immobilized artificial membrane chromatography, and prodrug activation was tested in the brain tissue of experimental animals. Esters of pGlu-Glu-Pro-NH2 with long-chain primary alcohols emerged as potentially useful prodrugs to improve the central nervous system activity of pGlu-Glu-Pro-NH2 upon systemic administration, as revealed by the enhancement of analeptic activity in mice.
AB - Potential prodrugs for the TRH-like tripeptide pGlu-Glu-Pro-NH2 were synthesized either by esterifying the Glu side-chain of the parent peptide in solution with alcohols in the presence of resin-bound dicyclohexylcarbodiimide or by solid-phase peptide chemistry. Affinities of these ester prodrugs to lipid membranes as predictors of the transport across the blood-brain barrier were compared by immobilized artificial membrane chromatography, and prodrug activation was tested in the brain tissue of experimental animals. Esters of pGlu-Glu-Pro-NH2 with long-chain primary alcohols emerged as potentially useful prodrugs to improve the central nervous system activity of pGlu-Glu-Pro-NH2 upon systemic administration, as revealed by the enhancement of analeptic activity in mice.
UR - http://www.scopus.com/inward/record.url?scp=0037463764&partnerID=8YFLogxK
U2 - 10.1016/S0960-894X(03)00081-7
DO - 10.1016/S0960-894X(03)00081-7
M3 - Article
C2 - 12643900
AN - SCOPUS:0037463764
SN - 0960-894X
VL - 13
SP - 1011
EP - 1014
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 6
ER -