Amphiphilic derivatives of thioether containing block copolypeptides

Patent metadata

Field	Value
Publication number	US-9718921-B2
Application number	US-201414770417-A
Country	US
Kind code	B2
Filing date	Feb 26, 2014
Priority date	Feb 26, 2013
Publication date	Aug 1, 2017
Grant date	Aug 1, 2017

Abstract

Methods for preparation of novel amphiphilic derivatives of thioether containing block copolypeptides with narrow chain length distributions are described. These block copolymers can be chemically modified by oxidation and alkylation of the thioether containing residues. These materials generate self-assembled micelles, vesicles and hydrogels, or emulsions with oil phases. These assemblies can be used to encapsulate and delivery therapeutic molecules. The assemblies can be taken up by cells to release molecules from the assemblies.

First claim

What is claimed is:

1. A process for preparing an amphiphilic block copolypeptide with oxidized thioether groups comprising:
synthesizing a block copolypeptide wherein at least one of the blocks contains at least 3 consecutive hydrophobic amino acids selected from leucine, phenylalanine, alanine, isoleucine, valine, tyrosine, and tryptophan, and wherein at least one of the blocks contains at least 3 consecutive thioether containing amino acids selected from methionine, S-methyl-cysteine, S-ethyl-cysteine, S-allyl-cysteine, S-benzyl-cysteine, S-farnesyl-cysteine, S-propargyl-cysteine, S-methyl-homocysteine, S-ethyl-homocysteine, S-allyl-homocysteine, S-benzyl-homocysteine, S-farnesyl-homocysteine, and S-propargyl-homocysteine;
adding an oxidizing reagent to the block copolypeptide; and
reacting the block copolypeptide so that the majority of the thioether groups in the polypeptide are oxidized, thereby forming the amphiphilic block copolypeptide with oxidized thioether groups.

2. The process of claim 1 , wherein the thioether containing amino acids are methionine.

3. The process of claim 1 , wherein the thioether containing amino acids are one or more of S-methyl-cysteine, S-ethyl-cysteine, S-allyl-cysteine, S-benzyl-cysteine, S-farnesyl-cysteine, and S-propargyl-cysteine.

4. The process of claim 1 , wherein the thioether containing amino acids are one or more of the following: S-methyl-homocysteine, S-ethyl-homocysteine, S-allyl-homocysteine, S-benzyl-homocysteine, S-farnesyl-homocysteine, and S-propargyl-homocysteine.

5. The process of claim 1 , wherein the oxidized thioether groups in the amphiphilic block copolypeptide are one or more of the following: sulfoxide, and sulfone.

6. The process of claim 1 wherein the hydrophobic amino acids are one or more of L-leucine, L-phenylalanine, L-alanine, L-isoleucine, L-valine, L-tyrosine, and L-tryptophan.

7. The process of claim 1 , wherein the block copolypeptide is a diblock copolypeptide.

8. The process of claim 1 , wherein the block copolypeptide is a triblock copolypeptide.

9. The process of claim 1 , wherein the thioether containing amino acids are L-methionine.

10. The process of claim 1 , wherein the hydrophobic amino acids are L-leucine or L-phenylalanine.

11. The process of claim 1 , wherein the oxidizing reagent comprises H 2 O 2 .

12. The process of claim 1 , wherein the amphiphilic block copolypeptide with oxidized thioether groups is
poly(L-methionine-sulfoxide) 65 -block-poly(L-leucine 0.5 -co-L-phenylalanine 0.5 ) 20 ;
poly(Nε-trifluoroacetyl-L-lysine) 11 -block-poly(L-methionine sulfoxide) 55 -block-poly(L-leucine 0.5 -co-L-phenylalanine 0.5 ) 20 ;
poly(Nε-trifluoroacetyl-L-lysine) 21 -block-poly(L-methionine sulfoxide) 55 -block-poly(L-leucine 0.5 -co-L-phenylalanine 0.5 ) 20 ;
poly(L-lysine) 10 -block-poly(L-methionine sulfoxide) 55 -block-poly(L-leucine 0.5 -co-L-phenylalanine 0.5 ) 20 ;
poly(L-lysine) 20 -block-poly(L-methionine sulfoxide) 55 -block-poly(L-leucine 0.5 -co-L-phenylalanine 0.5 ) 20 ;
poly(L-homoarginine) 10 -block-poly(L-methionine sulfoxide) 55 -block-poly(L-leucine 0.5 -co-L-phenylalanine 0.5 ) 20 ; or
poly(L-homoarginine) 20 -block-poly(L-methionine sulfoxide) 55 -block-poly(L-leucine 0.5 -co-L-phenylalanine 0.5 ) 20 .

Assignees

• Univ California

Inventors

• Deming Timothy J
• Kramer Jessica R
• Rodriguez April R

Classifications

• A61K47/42 Primary

  Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34) · CPC title

• A61K47/34

  Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence) · CPC title

• C08G69/48 Primary

  Polymers modified by chemical after-treatment · CPC title

• C08G69/10

  Alpha-amino-carboxylic acids {(polysuccinimides C08G73/1092)} · CPC title

• C08G69/42

  Polyamides containing atoms other than carbon, hydrogen, oxygen, and nitrogen (C08G69/12, C08G69/32 take precedence) · CPC title