# US 7,608,582 B2 · Delivery vehicle comprising a modified MscL protein channel > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,608,582 B2 - Document ID: US7608582B2 - Status: Granted - Kind: B2 - Application number: 11/978,743 - Filed: 2007-10-29 - Published: 2008-06-12 - Granted: 2009-10-27 - Earliest claimed: 2003-11-25 - Assignees: Applied NanoSystems B.V. - Inventors: Armagan Kocer; Martin Walko; George Thomas Robillard - Web page: https://patentgrep.com/patent/US7608582B2 ## CPC - A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant - A61K 9/1271: Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) - A61K 47/6911: {the form being a liposome} - A61P 35/00: Antineoplastic agents - C07C 381/04: Thiosulfonates - Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## Abstract The invention relates to the field of drug delivery, in particular, to compounds and methods for the chemical modification of a proteinaceous channel to be used in pharmaceutical delivery vehicles for controlled and/or localized release of therapeutic molecules (e.g., small molecules, peptides, proteins or other macromolecules). Provided are drug delivery vehicles comprising a pH- and/or light-responsive channel protein. ## Claims ### Claim 1 A delivery vehicle for controlled and/or localized release of therapeutic molecules, said delivery vehicle comprising a channel protein, the channel protein modified with a pH-responsive or light-responsive compound of the general formula Q-C or P-C, wherein Q is a chargeable group selected from the group consisting of Q1, Q2, and Q3 as depicted in the following, wherein R1, R2 and R3 are independently selected from the group consisting of H, methyl (Me), ethyl (Et), propyl (Pr), isopropyl (iPr), phenyl (Ph), and benzyl (Bn), wherein P is a photocleavable chargeable group selected from the group consisting of P1, P2, P3, P4, P5, P6, P7 and P8 as depicted in the following, wherein R1 and R2 are independently selected from the group of H, Me, Et, Pr, iPr, Ph and Bn and wherein R3═H or OMe, and wherein C is a coupling group selected from the group consisting of C1, C2, C3, C4, C5 and C6 as depicted in the following, wherein X═Br or I. ### Claim 2 (depends on 1) The delivery vehicle of claim 1, wherein group Q or group P is connected to group C via a linker group L selected from the linker groups consisting of L1, L2, L3 and L4 as depicted in the following, wherein n=1-10 and m=1-3. ### Claim 3 (depends on 1) The delivery vehicle of claim 1, further comprising a therapeutic molecule. ### Claim 4 (depends on 1) The delivery vehicle of claim 1, wherein the pH-responsive or light-responsive compound is attached via coupling group C to a cysteine residue of the modified channel protein. ### Claim 5 (depends on 4) The delivery vehicle of claim 4, wherein the cysteine residue is located in a region that corresponds to amino acid residues 1-14, residues 15-45, residues 46-75 or residues 76-100 of the MscL protein of E. coli. ### Claim 6 (depends on 1) The delivery vehicle of claim 1, wherein the modified channel protein is a mechanosensitive channel of large conductance (MscL). ### Claim 7 (depends on 1) The delivery vehicle of claim 1, wherein the modified channel protein is a modified channel protein of a prokaryote, E. coli, or Lactococcus lactis. ### Claim 8 A delivery vehicle comprising a protein, the protein modified with a pH-responsive or light-responsive compound of the general formula Q-C or P-C, wherein Q is a chargeable group selected from the group consisting of Q1, Q2, and Q3 as depicted in the following, wherein R1, R2 and R3 are independently selected from the group consisting of H, methyl (Me), ethyl (Et), propyl (Pr), isopropyl (iPr), phenyl (Ph) and benzyl (Bn), wherein P is a photocleavable chargeable group selected from the group consisting of P1, P2, P3, P4, P5, P6, P7 and P8 as depicted in the following, wherein R1 and R2 are independently selected from the group consisting of H, Me, Et, Pr, iPr, Ph and Bn and wherein R3═H or OMe, and wherein C is a coupling group selected from the group consisting of C1, C2, C3, C4, C5 and C6 as depicted in the following, wherein X═Br or I. ### Claim 9 (depends on 8) The delivery vehicle of claim 8, wherein the protein comprises a channel protein. ### Claim 10 (depends on 8) The delivery vehicle of claim 8, further comprising a proteoliposome. ### Claim 11 (depends on 8) The delivery vehicle of claim 8, further comprising a therapeutic molecule. ### Claim 12 (depends on 8) The delivery vehicle of claim 8, further comprising a dye. ### Claim 13 (depends on 8) The delivery vehicle of claim 8, wherein group Q or Group P is connected to group C via a linker group L selected from the linker groups consisting of L1, L2, L3 and L4 as depicted in the following, wherein n=1-10 and m=1-3. ### Claim 14 A delivery vehicle comprising a protein, the protein modified with a compound of the general formula Q-C or P-C, wherein Q is selected from the group consisting of Q, Q2, and Q3 as depicted in the following, wherein R1, R2 and R3 are independently selected from the group consisting of H, methyl (Me), ethyl (Et), propyl (Pr), isopropyl (iPr), phenyl (Ph) and benzyl (Bn), wherein P is a photocleavable chargeable group selected from the group consisting of P1, P2, P3, P4, P5, P6, P7 and P8 as depicted in the following, wherein R1 and R2 are independently selected from the group consisting of H, Me, Et, Pr, iPr, Ph and Bn and wherein R3═H or OMe, and wherein C is a coupling group selected from the group consisting of C1, C2, C3, C4, C5 and C6 as depicted in the following, wherein X═Br or I. ### Claim 15 (depends on 14) The delivery vehicle of claim 14, wherein group Q or group P is connected to group C via a group L selected from the group consisting of L1, L2, L3 and L4 as depicted in the following, wherein n=1-10 and m=1-3. ### Claim 16 (depends on 1) A pharmaceutical composition comprising a delivery vehicle of claim 1. ### Claim 17 (depends on 1) A method of controlling the release of a therapeutic molecule at a target site of a subject, said method comprising loading the delivery vehicle of claim 1 with a therapeutic molecule, introducing the loaded delivery vehicle into the subject for delivery to the target site, and triggering the release of said therapeutic molecules. ### Claim 18 (depends on 17) The method according to claim 17, wherein said triggering comprises exposure to a low pH. ### Claim 19 (depends on 17) The method according to claim 17, wherein said triggering comprises illumination and then exposure to a low pH.