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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 ?M. 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.

SUBMITTER: Meinander K

PROVIDER: S-EPMC4027621 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Replacement of the Disulfide Bridge in a KLK3-Stimulating Peptide Using Orthogonally Protected Building Blocks.

Meinander Kristian K Pakkala Miikka M Weisell Janne J Stenman Ulf-Håkan UH Koistinen Hannu H Närvänen Ale A Wallén Erik A A EA

ACS medicinal chemistry letters 20131216 2

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 we ...[more]

PMID: 24900791

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