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Dual system for the central nervous system targeting and blood‐brain barrier transport of a selective prolyl oligopeptidase inhibitor
Author(s) -
Teixidó Meritxell,
Zurita Esther,
Mendieta Laura,
OllerSalvia Benjamí,
Prades Roger,
Tarragó Teresa,
Giralt Ernest
Publication year - 2013
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.22275
Subject(s) - blood–brain barrier , chemistry , central nervous system , oligopeptidase , selection (genetic algorithm) , combinatorial chemistry , pharmacology , biophysics , biochemistry , enzyme , neuroscience , computer science , artificial intelligence , medicine , biology
Less than 2% of all potential neurotherapeutics cross the blood‐brain barrier (BBB). Here, we sought to build a construct with the capacity to cross this barrier, to behave as a chemical delivery system, and, once inside the central nervous system, to be transformed and then act as an enzyme inhibitor. With all this in mind, here, we describe the entire process to obtain such a compound, from the initial candidate selection to preparation of the compound library and posterior evaluation and final selection of the most promising candidates in terms of selectivity, serum stability, and BBB‐transport. © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 100: 662–674, 2013.