C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
C12N 15/52 (2006.01) C12N 9/00 (2006.01) C12N 9/10 (2006.01) C12N 15/54 (2006.01) C12N 15/62 (2006.01) C12P 13/04 (2006.01) C12P 21/02 (2006.01)
Patent
CA 2377592
The invention relates to a method of modifying peptide synthetases in such a manner that they can N-methylate their substrate amino acids. PPS are enzymes that synthesize peptides in a non-ribosomal manner. PPS have a modular set-up. Each module has an activation domain which recognizes and covalently binds to the respective substrate amino acid. The peptide synthesis catalyzed by PPS proceeds by the condensation of the covalently bound substrate amino acids. A minor number of the known activation domains is capable of also N-methylating the bound substrate amino acids. The inventive method allows conversion of the activation domains without N-methyl transferase activity to activation domains with N-methyl transferase activity while maintaining the original substrate specificity.
L'invention concerne la modification des synthétases de peptides (PPS) de manière qu'elles puissent N-méthyler leurs acides aminés de substrat. Les PPS sont des enzymes qui synthétisent des peptides de manière non ribosomale. Les PPS possèdent une structure modulaire. Chaque module comporte un domaine d'activation, qui reconnaît l'acide aminé du substrat correspondant et le lie par covalence. La synthèse des peptides, catalysée par les PPS, s'effectue ensuite par condensation des acides aminés de substrat liés par covalence. Un nombre réduit de domaines d'activation connus est capable de N-méthyler les acides aminés de substrat liés. Ladite invention permet de transformer les domaines d'activation sans activité de N-méthyltransférase en des domaines d'activation possédant une activité de N-méthyltransférase, tout en conservant leur spécificité de substrat.
Keller Ullrich
Schauwecker Florian
Actinodrug Pharmaceuticals Gmbh
Blake Cassels & Graydon Llp
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