Cellular transport system for transferring a sulfonic acid construct carrying a cargo into the cytoplasm of a cell

A cellular transport system for bringing a sulfonic acid construct of the following formula (I) or a physiologically acceptable salt thereof

• wherein:
• L1 is a group —(CH2)1-6—, wherein said group —(CH2)1-6— is optionally substituted with one or more groups RL11, and further wherein one or more —CH2— units comprised in said group —(CH2)1-6— are each optionally replaced by a group RL12;
• L2 is —C(═O)— or —C(═S)—;
• X is a chemical moiety which is attached to L2 via a heteroatom comprised in said chemical moiety, wherein said heteroatom is selected from oxygen, sulfur, nitrogen and selenium;
• each RL11 is independently selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, —(C0-3 alkylene)-OH, —(C0-3 alkylene)-O(C1-5 alkyl), —(C0-3 alkylene)-O(C1-5 alkylene)-OH, —(C0-3 alkylene)-O(C1-5 alkylene)-O(C1-5 alkyl), —(C0-3 alkylene)-SH, —(C0-3 alkylene)-S(C1-5 alkyl), —(C0-3 alkylene)-S(C1-5 alkylene)-SH, —(C0-3 alkylene)-S(C1-5 alkylene)-S(C1-5 alkyl), —(C0-3 alkylene)-NH2, —(C0-3 alkylene)-NH(C1-5 alkyl), —(C0-3 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), —(C0-3 alkylene)-halogen, —(C0-3 alkylene)-(C1-5 haloalkyl), —(C0-3 alkylene)-O—(C1-5 haloalkyl), —(C0-3 alkylene)-CF3, —(C0-3 alkylene)-CN, —(C0-3 alkylene)-NO2, —(C0-3 alkylene)-CHO, —(C0-3 alkylene)-CO—(C1-5 alkyl), —(C0-3 alkylene)-COOH, —(C0-3 alkylene)-CO—O—(C1-5 alkyl), —(C0-3 alkylene)-O—CO—(C1-5 alkyl), —(C0-3 alkylene)-CO—NH2, —(C0-3 alkylene)-CO—NH(C1-5 alkyl), —(C0-3 alkylene)-CO—N(C1-5 alkyl)(C1-5 alkyl), —(C0-3 alkylene)-NH—CO—(C1-5 alkyl), —(C0-3 alkylene)-N(C1-5 alkyl)-CO—(C1-5 alkyl), —(C0-3 alkylene)-SO2—NH2, —(C0-3 alkylene)-SO2—NH(C1-5 alkyl), —(C0-3 alkylene)-SO2—N(C1-5 alkyl)(C1-5 alkyl), —(C0-3 alkylene)-NH—SO2—(C1-5 alkyl), —(C0-3 alkylene)-N(C1-5 alkyl)-SO2—(C1-5 alkyl), —(C0-3 alkylene)-carbocyclyl, and —(C0-3 alkylene)-heterocyclyl, wherein the carbocyclyl moiety comprised in said —(C0-3 alkylene)-carbocyclyl and the heterocyclyl moiety comprised in said —(C0-3 alkylene)-heterocyclyl are each optionally substituted with one or more groups RL15, and further wherein any two groups RL11 that are attached to different carbon atoms comprised in L1 may also be mutually linked to form together a group —RL13—, and wherein any two groups RL11 that are attached to the same carbon atom comprised in L1 may also be mutually linked to form, together with the carbon atom that they are attached to, a cycloalkyl or a heterocycloalkyl, wherein said cycloalkyl or said heterocycloalkyl is optionally substituted with one or more groups RL15;
• each RL12 is independently selected from —O—, —CO—, —C(═O)O—, —O—C(═O)—, —N(RL14)—, —N(RL14)—CO—, —CO—N(RL14)—, —S—, —SO—, —SO2—, —SO2—N(RL14)— and —N(RL14)—SO2—;
• each RL13 is independently selected from C1-6 alkylene and C2-6 alkenylene, wherein said alkylene or said alkenylene is optionally substituted with one or more groups independently selected from C1-4 alkyl, —OH, —O(C1-4 alkyl), —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)(C1-4 alkyl), halogen, —CF3, and —CN, and further wherein one or more —CH2— units comprised in said alkylene or in said alkenylene are each optionally replaced by a group independently selected from —O—, —CO—, —NH—, —N(C1-5 alkyl)- and —S—;
• each RL14 is independently selected from hydrogen and C1-5 alkyl;
• and
• each RL15 is independently selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, —(C0-3 alkylene)-OH, —(C0-3 alkylene)-O(C1-5 alkyl), —(C0-3 alkylene)-O(C1-5 alkylene)-OH, —(C0-3 alkylene)-O(C1-5 alkylene)-O(C1-5 alkyl), —(C0-3 alkylene)-SH, —(C0-3 alkylene)-S(C1-5 alkyl), —(C0-3 alkylene)-S(C1-5 alkylene)-SH, —(C0-3 alkylene)-S(C1-5 alkylene)-S(C1-5 alkyl), —(C0-3 alkylene)-NH2, —(C0-3 alkylene)-NH(C1-5 alkyl), —(C0-3 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), —(C0-3 alkylene)-halogen, —(C0-3 alkylene)-(C1-5 haloalkyl), —(C0-3 alkylene)-O—(C1-5 haloalkyl), —(C0-3 alkylene)-CF3, —(C0-3 alkylene)-CN, —(C0-3 alkylene)-NO2, —(C0-3 alkylene)-CHO, —(C0-3 alkylene)-CO—(C1-5 alkyl), —(C0-3 alkylene)-COOH, —(C0-3 alkylene)-CO—O—(C1-5 alkyl), —(C0-3 alkylene)-O—CO—(C1-5 alkyl), —(C0-3 alkylene)-CO—NH2, —(C0-3 alkylene)-CO—NH(C1-5 alkyl), —(C0-3 alkylene)-CO—N(C1-5 alkyl)(C1-5 alkyl), —(C0-3 alkylene)-NH—CO—(C1-5 alkyl), —(C0-3 alkylene)-N(C1-5 alkyl)-CO—(C1-5 alkyl), —(C0-3 alkylene)-SO2—NH2, —(C0-3 alkylene)-SO2—NH(C1-5 alkyl), —(C0-3 alkylene)-SO2—N(C1-5 alkyl)(C1-5 alkyl), —(C0-3 alkylene)-NH—SO2—(C1-5 alkyl), and —(C0-3 alkylene)-N(C1-5 alkyl)-SO2—(C1-5 alkyl);
• into a cell and releasing a cargo from the sulfonic acid construct of formula (I) in the cell's cytoplasm, wherein said cargo is a compound H—X wherein X is as defined in formula (I), and wherein the cellular transport system comprises:
• (i) a sulfonate transporter located in the membrane of the cell wherein said sulfonate transporter is capable of transporting the sulfonic acid construct of formula (I) across the cytoplasm membrane into the cytoplasm;
• and
• (ii) a γ-glutamyl transferase (GGT;
• EC 2.3.2.2) which is modified to be located in the cytoplasm of the cell, wherein said γ-glutamyl transferase is capable of hydrolyzing the sulfonic acid construct of formula (I) to release the compound H—X.