US2004043939A1PendingUtilityA1
Peptide-based gemini compounds
Est. expiryDec 9, 2017(expired)· nominal 20-yr term from priority
A61K 47/641C07K 5/0606C12N 15/88C07K 5/1019C07K 5/0815A61K 48/00A61P 31/04
54
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
New peptide-based gemini compounds comprising two linked chains: each chain having: (1) a positively charged hydrophilic head, Q 1 or Q 2 , formed from one or more amino acids and/or amines (2) a central portion, P 1 or P 2 , having a polypeptide backbone, and (3) a hydrophobic tail, R 1 or R 2 , the central sections of each chain being linked together by bridge Y through residues in P 1 and P 2 , are disclosed. Methods for their preparation and uses are also disclosed. Such uses include transfection of polynucleotides into cells in-vivo and in-vitro.
Claims
exact text as granted — not AI-modified1 . A peptide-based gemini compound comprising two linked chains:
each chain having:
(1) a positively charged hydrophilic head, Q 1 or Q 2 , formed from one or more amino acids and/or amines
(2) a central portion, P 1 or P 2 , having a polypeptide backbone, and
(3) a hydrophobic tail, R 1 or R 2 ,
the central sections of each chain being linked together by bridge Y through residues in P 1 and P 2 .
2 . A peptide-based gemini compound according to claim 1 which has the formula (I):
where:
A 1 and A 5 ,which may be the same or different, is a positively charged group formed from one or more amino acids or amines joined together in a linear or branched manner; A 2 /A 6 CH(NH)CO, which may be the same or different, is derived from an amino acid;
p and q, which may be the same or different, is 0 or 1;
X 1 /X 2 CH 2 CH(NH)CO, which may be the same or different, is derived from cysteine (X 1 /X 2 ═S), serine or threonine (X 1 /X 2 ═O);
A 4 /A 8 CH(NH)CO, which may be the same or different, is derived from serine or threonine;
Y is a linker group or a disulphide bond when X 1 and X 2 is each S;
R 1 and R 2 are C (10-20) saturated or unsaturated alkyl groups, and W and Z are NH, O, CH 2 or S; or
a salt thereof.
3 . A peptide-based gemini compound according to claim 2 wherein the A 1 and A 5 groups are bonded by an amide (CONH) bond.
4 . A compound according to claims 2 or 3 wherein A 1 /A 5 are D- or L-amino acids selected from arginine, lysine, ornithine and histidine.
5 . A compound according to claims 2 to 4 wherein A 1 /A 5 have up to 7 amino acids linked in a linear or branched chain.
6 . A compound according to claim 5 wherein A 1 /A 5 have two or three lysines or ornithines or a combination of lysine, ornithine, arginine and histidine.
7 . A compound according to any one of claims 2 to 6 wherein the amino acid from which the A 2 /A 6 CH(NH)CO is derived is serine.
8 . A compound according to any one of claims 2 to 7 wherein Y is (CH 2 ) m , where m is an integer from 1 to 6.
9 . A compound according to any one of claims 2 to 7 wherein Y is a disulphide bond when X 1 and X 2 is each S.
10 . A compound according to claim 8 or 9 wherein m is 2.
11 . A compound according to any one of claims 2 to 10 wherein R is C 12 alkyl.
12 . A compound according to any one of claims 2 to 11 wherein W and Z are NH.
13 . A compound according to any one of claims 2 to 12 wherein the salt is a pharmaceutically acceptable salt.
14 . A compound according to any one of claims 1 to 13 which is symmetrical, that is A 1 and A 5 are the same, A 2 and A 6 are the same, A 4 and A 8 are the same, R 1 and R 2 are the same, and W and Z are the same.
15 . Compound 39: 2-amino-3-{2-[2-amino-2-( 1-dodecylcarbamoyl-2-hydroxy-ethylcarbamoyl)-ethylsulphanyl]-ethylsulphonyl}-N-(1-dodecylcarbamoyl-2-hydroxy-ethyl-)-propionamide, and derivatives thereof, compounds 40 to 58.
16 . The compound:
17 . The compound:
18 . The compound:
19 . The compound:
20 . The compound:
21 . The use of a gemini-based peptide compound as defined in any one of claims 1 to 20 in enabling transfection of DNA or RNA or analogs thereof into a eukaryotic or prokaryotic cell in vivo or in vitro.
22 . The use of a peptide-based gemini compound according to claim 21 wherein the compound is used in combination with one or more supplements selected from the group consisting of:
(i) a neutral carrier; or
(ii) a complexing reagent.
23 . The use according to claim 22 wherein the neutral carrier is dioleyl phosphatidylethanolamine (DOPE).
24 . The use according to claim 22 wherein the complexing reagent is PLUS reagent.
25 . The use according to claim 22 wherein the complexing reagent is a peptide comprising mainly basic amino acids.
26 . The use according to claim 25 wherein the peptide consists of basic amino acids.
27 . The use according to claim 25 or 26 wherein the basic amino acids are selected from lysine and arginine.
28 . The use according to claim 26 wherein the peptide is polylysine or polyornithine.
29 . A method of transfecting polynucleotides into cells in vivo for gene therapy, which method comprises administering peptide-based gemini compounds of any one of claims 1 to 20 together with, or separately from, the gene therapy vector.
30 . The use of a peptide-based gemini compound of any one of claims 1 to 20 to facilitate the transfer of a polynucleotide or an anti-infective compounds into prokaryotic or eukaryotic organism for use in anti-infective therapy.
31 . The use of a peptide-based gemini compound of any one of claims 1 to 20 to facilitate the adhesion of cells in culture to each other or to a solid or semi-solid surface.
32 . A process for preparing peptide-based gemini compounds of claim 1 or 2 which process comprises adding amino acids or peptides to 2-amino-3-{2-[2-amino-2-(1-dodecylcarbamoyl-2-hydroxy-ethylcarbamoyl)-ethylsulphanyl]-ethylsulphonyl}-N-(1-dodecylcarbamoyl-2-hydroxy-ethyl-)-propionamide.Join the waitlist — get patent alerts
Track US2004043939A1 — get alerts on status changes and closely related new filings.
We store only your email — no account needed. See our privacy policy.