Proteinoid compounds, process of preparing same and uses thereof

Patent metadata

Field	Value
Publication number	US-2023414529-A1
Application number	US-202318204576-A
Country	US
Kind code	A1
Filing date	Jun 1, 2023
Priority date	Aug 10, 2015
Publication date	Dec 28, 2023
Grant date	—

Abstract

Proteinoid compounds characterized by a molecular weight (Mw) of at least 15,000 Da, processes of preparing such compounds and methods of use thereof, are provided. A method of monitoring the presence and metastases of cancer in a body of an individual is further disclosed.

First claim

1 . A composition comprising proteinoid compounds in a form of self-assembled hollowsphere particles, wherein a hydrodynamic size of at least 80% of the self-assembled hollowsphere particles varies by less than 25% from an average hydrodynamic diameter of the entire self-assembled hollowsphere particles of the composition; wherein each of said proteinoid compounds is a random amino acid co-polymer, and wherein said proteinoid compounds are characterized by a dispersity index (1)) value of less than 1.3 and by a weight average molecular weight (Mw) of at least 15,000 Da; and wherein said random amino acid co-polymer is characterized by an IR spectrum devoid of a carbonyl stretching peak above 1700 cm −1 .

2 . The composition of claim 1 , wherein said random amino acid co-polymer consists of alpha-amino acid residues bound to each other via a primary amide bond, wherein the amino acid residue is selected from the group consisting of: val, ala, arg, asn, asp, cys, glu, gln, gly, his, met, ile, leu, lys, phe, pro, ser, thr, trp, and tyr residue.

3 . The composition of claim 1 , further comprising one or more agents selected from: labeling compound, UV blocker, an antibacterial compound, a magnetite, an antioxidant, a filler, biologically active agent, said one or more agents being attached to and/or encapsulated within said self-assembled hollowsphere.

4 . The composition of claim 1 , wherein said random amino acid co-polymer is represented by Formula 1:

wherein R represents an amino acid residue selected from the group consisting of: val, ala, arg, asn, asp, cys, glu, gln, gly, his, met, ile, leu, lys, phe, pro, ser, thr, trp, and tyr residue.

5 . The composition of claim 1 , wherein the polymeric backbone is represented by the following formula: [A 1 ] x [A 2 ] y [A 3 ] z wherein: a) A 1 , is selected from Glu, Asp and Lys; b) A 2 and A 3 each independently represents an amino acid residue selected from the group consisting of: val, ala, arg, asn, asp, cys, glu, gln, gly, his, met, ile, leu, lys, phe, pro, ser, thr, trp, and tyr residue; or wherein A 2 or A 3 is absent; c) x, y, and z are integers, independently, representing the total numbers of A 1 , A 2 , and A 3 , respectively, in said polymeric backbone, such that x+y+z has a value of at least 100.

6 . The composition of claim 5 , wherein A 2 , and A 3 are each, independently selected from Asp, Arg, Tyr, His, Ala, Phe, Cys, and Ile residue.

7 . The composition of claim 5 , wherein A 1 is Glu and A 2 is selected form Asp, Phe, and Lys, and A 3 is absent.

8 . The composition of claim 5 , wherein A 1 is Glu, A 2 is Lys, and A 3 is Phe or is absent.

9 . The composition of claim 5 , wherein x, y, and z have a value such that at least one of: x/y, x/z, and y/z ranges from about 1:3 to about 3:1.

10 . The composition of claim 1 , wherein said random amino acid co-polymer is represented by the following formula [Phe] n [Arg] x [His] y [Lys] z n, x, y, and z are integers, independently, representing the total numbers of Phe, Arg, His, and Lys, respectively, in the polymeric backbone, such that n+x+y+z has a value of at least 100.

11 . The composition of claim 1 , wherein said proteinoid compounds are characterized by a dispersity index (1)) value of less than 1.1.

12 . The composition of claim 11 , wherein said proteinoid compounds are characterized by a weight average molecular weight (Mw) of at least 30,000 Da.

13 . The composition of claim 11 , wherein said proteinoid compounds are characterized by a weight average molecular weight (Mw) of between 30,000 and 300, 000 Da.

14 . A process of synthesizing the self-assembled hollowsphere particles of claim 1 , the process comprising:
a) heating one or more types of amino acid to a temperature that ranges from 100° C. to 200° C. under inert gas atmosphere, thereby forming a melt; b) stirring said melt at a temperature that ranges from 100° C. to 200° C., for at least 30 min, thereby polymerizing said one or more amino acids thereby obtaining a crude mixture; c) purifying said crude mixture to obtain a solution comprising purified proteinoid compounds; and d) heating said solution to a temperature sufficient for inducing self-assembly of the purified proteinoid compounds, thereby obtaining said self-assembled hollowsphere particles; wherein said one or more types of amino acid comprise at least one of Glu, Asp and Lys.

15 . The process of claim 14 , wherein said purifying is selected from dialysis, filtration and chromatographic separation.

16 . The process of claim 14 , wherein said purified proteinoid compounds are soluble in water so as to obtain a solution.

17 . The process of claim 16 , wherein all of said purified proteinoid compounds are dissolved within said solution at a concentration of at least 1 mg/ml, and wherein a temperature of said solution ranges between 20° C. and 30° C.

Assignees

• Univ Bar Ilan

Inventors

• Margel Shlomo
• Kolitz Domb Michal
• Kiel Stella
• Sason Elisheva

Classifications

• A61K9/5169 Primary

  Proteins, e.g. albumin, gelatin · CPC title

• A61K49/0043

  Fluorescein, used in vivo · CPC title

• A61K49/0056

  Peptides, proteins, polyamino acids · CPC title

• C08G63/6852

  derived from hydroxy carboxylic acids · CPC title

• A61K49/0032

  Methine dyes, e.g. cyanine dyes · CPC title