1. Process for obtaining polyglutamates by means of controlled polymerization of N-carboxyanhydrides (NCAs) of alpha-amino acids using non-nucleophilic salts as initiator: tetrafluoroborate, according to formula:
wherein:
R represents an alkyl group with Defined C-terminal attachment group (alkyne, azyde, thiols, halydes, activated thiols, alkenes, activated esters, activated alcohols, protected amines, maleimide groups, acetals, activated carboxylic acids), ethylenglycol (EG) of different molecular weights including polyethylenglycol (PEG, from 100 to 20000 gmol); and
n represents number of units of \u03b3-benzylglutamate in the polymer, from 1 to 1000.
2. The process according to claim 1, wherein tetrafluoroborate is ammonium tetrafluoroborate.
3. The process according to claim 1, wherein R is n-butylamine.
4. The process according to claim 1, wherein R is polyethyleneglycol.
5. The process according to claim 1, obtaining final product in di-block form. Details of the synthesis are shown in the formula below:
wherein:
represents an alkyl group with Defined C-terminal attachment group (alkyne, azyde, thiols, halydes, activated thiols, alkenes, activated esters, activated alcohols, protected amines, maleimide groups, acetals, activated carboxylic acids), ethylenglicol (EG) of different molecular weights including polyethylenglycol (PEG, from 100 to 20000 gmol);
R3 represents an alkyl group with Defined C-terminal attachment group (alkyne, azyde, thiols, halydes, activated thiols, alkenes, activated esters, activated alcohols, protected amines, maleimide groups, acetals, activated carboxylic acids), ethylenglicol (EG) of different molecular weights including polyethylenglycol (PEG, from n=2 to n=16); amino acids such as lysine, arginine, imidazole, histidine and cysteine, and secondary and tertiary amino groups;
x represents the number of monomer units included into R1 definition, from 1 to 500;
y represents the number of glutamic units modified with R3 group in the polymer, from 1 to 1000; and
z represents the number of glutamic units without modification in the polymer, from 1 to 1000.
6. The process according to claim 1, obtaining final product in tri-block form. Details of the synthesis are shown in the formula bellow:
wherein:
R1 represents an alkyl group with Defined C-terminal attachment group (alkyne, azyde, thiols, halydes, activated thiols, alkenes, activated esters, activated alcohols, protected amines,
maleimide groups, acetals, activated carboxylic acids), ethylenglicol (EG) of different molecular
weights including polyethylenglicol (PEG, from 100 to 20000 gmol);
R2 represents an alkyl group with Defined C-terminal attachment group (alkyne, azyde, thiols, halydes, activated thiols, alkenes, activated esters, activated alcohols, protected amines,
maleimide groups, acetals, activated carboxylic acids), ethylenglicol (EG) of different molecular
weights including polyethylenglycol (PEG, from 100 to 20000 gmol), PEG-thiol, PEG-4TP;
R3 represents an alkyl group with Defined C-terminal attachment group (alkyne, azyde, thiols, halydes, activated thiols, alkenes, activated esters, activated alcohols, protected amines,
maleimide groups, acetals, activated carboxylic acids), ethylenglycol (EG) of different molecular
weights including polyethylenglycol (PEG, from n=2 to n=16); amino acids such as lysine,
arginine, imidazole, histidine and cysteine, and secondary and tertiary amino groups;
x represents number of monomer units into definition R1, from 1 to 500;
y represents number of glutamic units modified with R3 group in the polymer, from 1 to 500;
z represents number of glutamic units not modified in the polymer, from 1 to 1000; and
p represents number of monomer units included into R3 definition, from 1 to 500.
7. The method according to claim 1, through the reaction between the di-blocks PEG-PGA previously obtained and a derivative of functionalized PEG with an activated carboxyl group, obtaining tri-block systems as seen in the formula bellow:
wherein
R1 represents an alkyl group with Defined C-terminal attachment group (alkyne, azyde, thiols, halydes, activated thiols, alkenes, activated esters, activated alcohols, protected amines, maleimide groups, acetals, activated carboxylic acids), ethylenglycol (EG) of different molecular weights including polyethylenglycol (PEG, from 100 to 20000 gmol);
R2 represents an alkyl group with Defined C-terminal attachment group (alkyne, azyde, thiols, halydes, activated thiols, alkenes, activated esters, activated alcohols, protected amines, maleimide groups, acetals, activated carboxylic acids), ethylenglycol (EG) of different molecular weights including polyethylenglycol (PEG, from 100 to 20000 gmol), PEG-thiol, PEG-4TP;
R3 represents an alkyl group with Defined C-terminal attachment group (alkyne, azyde, thiols, halydes, activated thiols, alkenes, activated esters, activated alcohols, protected amines, maleimide groups, acetals, activated carboxylic acids), ethylenglycol (EG) of different molecular eights including polyethylenglycol (PEG, from n=2 to n=16); amino acids such as lysine, arginine, imidazole, histidine and cysteine, and secondary and tertiary amino groups;
x represents number of monomer units into definition R1, from 1 to 500;
y represents number of glutamic units modified with R3 group in the polymer, from 1 to 500;
z represents number of glutamic units not modified in the polymer, from 1 to 1000; and
p represents number of monomer units included into R3 definition, from 1 to 500.
R2 and R3 can be used for the linking of bioactive agents (including low molecular weight drugs, peptides, proteins, antibodies), near infrared fluorescent probes, coordination complexes for MRI, PET and SPECT probes.
8. The process accordina to claim 1, in which once obtained the polyglutamate polymer its modified introducing polyethilenglycol chains in the polymeric chain, with the purpose of obtaining molecules that are capable of modifying the behaviour in vivo, the biodistribution and the therapeutic application of the corresponding bioactive agent
9. Polyglutamates obtained by the process defined in claim 1.
10. Drug delivery compound which comprises the polyglutamates of claim 9.
11. Molecular imaging diagnostic agent which comprises the polyglutamates of claim 9.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
What is claimed is:
1. A system for communication between a local host and a remote host that are connected by a network, the system comprising:
a device connected to the network and to the local host, said device including hardware logic for processing data packets,
a protocol processing stack disposed in the local host and configured for passing a communication control block to said device, with said communication control block defining a connection between the local host and the remote host,
wherein said device and said protocol processing stack are arranged such that a message transferred between said network and said local host is generally processed by said device instead of said protocol processing stack when said device is holding said communication control block.
2. The system of claim 1, wherein the device comprises means for processing TCP data packets.