Conjugates of soluble peptidic compounds with membrane-binding agents
AssigneeAdProTech Limited
InventorsRichard Anthony Godwin SMITH, Ian Dodd, Danuta Ewa Irena Mossakowkska
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Abstract
The present invention provides, among other things, soluble derivatives of soluble polypeptides that incorporate membrane binding elements. Methods of making these soluble derivatives, and methods of using these soluble derivatives also are provided.
Claims21
1-49. (canceled)
A membrane localization reagent for directing a molecule to an outer membrane of a cell, wherein the membrane localization reagent is soluble and comprises:
- (a) at least one lipophilic binding element comprising aliphatic acyl groups;
- (b) a hydrophilic peptide binding element comprising basic amino acids, wherein the hydrophilic binding element is bound to the lipophilic element;
- and
- (c) a linker that covalently binds (i) the molecule to be directed to the outer membrane of a cell to (ii) the hydrophilic peptide binding element of the membrane localization reagent.
A membrane localization reagent for directing a molecule to an outer membrane of a cell, wherein the membrane localization reagent is soluble and comprises a hydrophilic peptide binding element, wherein the peptide comprises a sequence selected from the group consisting of:
- (a) DGPKKKKKKSPSKSSG;
- (SEQ ID NO. 8)
- (b) GSSKSPSKKKKKKPGD;
- (SEQ ID NO. 9)
- (c) SPSNETPKKKKKRFSFKKSG;
- (SEQ ID NO. 10)
- (d) DGPKKKKKKSPSKSSK;
- (SEQ ID NO. 11)
- and
- (e) SKDGKKKKKKSKTK.
- (SEQ ID NO. 12)
The soluble compound according to 50, wherein the linker is selected from the group consisting of a cysteine residue;
- an N-haloacetyl group (where halo signifies chlorine, bromine or iodine);
- a haloacetyl group (where halo signifies chlorine, bromine or iodine) at an ε-amino group of a lysine residue;
- a bond;
- an amide group at the C-terminus;
- an N-terminal blocking group;
- and a fatty acid N-acyl group at the N-terminus or at an ε-amino group of a lysine residue.
A soluble derivative of a soluble polypeptide, wherein said derivative consisting of a conjugate or fusion of the polypeptide with a unit further consisting of two or more covalently linked heterologous membrane binding elements which elements are not all identical, which are capable of interacting independently with components of cellular or artificial membranes exposed to extracellular fluids and which are selected from the group consisting of:
- a) a membrane-insertive hydrophobic group selected from aliphatic acyl groups with between 8 and 18 methylene units and aliphatic amines with between 8 and 18 methylene units;
- b) a membrane-associative charged peptide consisting of between 3 and 25 amino acids of which no less than 2 and no more than 12 are basic residues;
- and
- c) a membrane component ligand further consisting of a peptide containing between 3 and 13 amino acids derived from known ligands for membrane components such as transmembrane proteins and identified by screening of chemical, bacteriophage, or other displayed libraries against specific membrane-derived molecular targets.
Dependencies are inferred from the claim text.