title: Replacement of the Disulfide Bridge in a KLK3-Stimulating Peptide Using Orthogonally Protected Building Blocks.
abstract: Peptide "B-2", which is one of the most potent kallikrein-related peptidase 3 (KLK3)-stimulating compounds, consists of 12 amino acids and is cyclized by a disulfide bridge between the N- and C-terminal cysteines. Orthogonally protected building blocks were used in the peptide synthesis to introduce a disulfide bridge mimetic consisting of four carbon atoms. The resulting pseudopeptides with alkane and E-alkene linkers doubled the proteolytic activity of KLK3 at a concentration of 14 μM. They were almost as potent as the parent "B-2" peptide, which gives a 3.6-fold increase in the proteolytic activity of KLK3 at the same concentration.
authors.affiliation: Division of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Helsinki , P.O. Box 56, FIN-00014 Helsinki, Finland.
authors.forename: Kristian
authors.initials: K
authors.lastname: Meinander
authors.affiliation: School of Pharmacy, University of Eastern Finland , P.O. Box 1627, FIN-70211 Kuopio, Finland.
authors.forename: Miikka
authors.initials: M
authors.lastname: Pakkala
authors.affiliation: School of Pharmacy, University of Eastern Finland , P.O. Box 1627, FIN-70211 Kuopio, Finland.
authors.forename: Janne
authors.initials: J
authors.lastname: Weisell
authors.affiliation: Department of Clinical Chemistry, Haartman Institute, University of Helsinki and Helsinki University Central Hospital , Haartmaninkatu 8, FIN-00290 Helsinki, Finland.
authors.forename: Ulf-Håkan
authors.initials: UH
authors.lastname: Stenman
authors.affiliation: Department of Clinical Chemistry, Haartman Institute, University of Helsinki and Helsinki University Central Hospital , Haartmaninkatu 8, FIN-00290 Helsinki, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Koistinen
authors.affiliation: School of Pharmacy, University of Eastern Finland , P.O. Box 1627, FIN-70211 Kuopio, Finland.
authors.forename: Ale
authors.initials: A
authors.lastname: Närvänen
authors.affiliation: Division of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Helsinki , P.O. Box 56, FIN-00014 Helsinki, Finland.
authors.forename: Erik A A
authors.initials: EA
authors.lastname: Wallén
keywords: Disulfide bridge mimetic; human kallikrein-related peptidase 3; peptide synthesis; prostate specific antigen; proteolytic activity; pseudopeptide