38 results about "N carboxyanhydride" patented technology

Methods and compositions for the generation of polypeptides having varied material properties are disclosed herein. Methods include means for initiating the polymerization of aminoacid-N-carboxyanhydride (NCA) monomer by combining the monomer with an amido-containing metallacycle, for making self assembling amphiphilic block copolypeptides and related protocols for adding oligo(ethyleneglycol) functionalized aminoacid-N-carboxyanhydrides (NCAs) to polyaminoacid chains. Additional methods include means of adding an end group to the carboxy terminus of a polyaminoacid chain by reacting an alloc-protected amino acid amide with a transition metal-donor ligand complex to forming an amido-amidate metallacycle for use in further polymerization reactions. Novel compositions for use in peptide synthesis and design including five and six membered amido-containing metallacycles and block copolypeptides are also disclosed.

This invention relates to a convenient and improved process for preparation of glatiramer acetate (copolymer-1) of pharmaceutical grade. The process involves polymerizing N-carboxyanhydrides of tyrosine, alanine, y-benzyl glutamate and ε-N-trifluoroacetyllysine in dioxane with diethylamine as initiator to afford protected copolymer-1. Treatment with hydrogen bromide in acetic acid at 35° C. for 3-5 h cleaves benzyl group to produce trifluoroacetyl copolymer-1. The trifluoroacetyl copolymer-1 is washed with an organic solvent to remove reactive benzyl bromide generated during debenzylation. Deprotection with aqueous piperidine, followed by dialysis offers glatiramer acetate (copolymer-1) of Molecular weight 5000-9000 daltons.

A method for synthesizing extended poly(amino acids) conjugated to imaging agents, such as DTPA, is disclosed. The amino acid is initially conjugated to the imaging agent at the monomer stage, followed by formation of the corresponding N-carboxyanhydride. The method utilizes catalyzed ring opening polymerization of the N-carboxyanhydride of the amino acid-imaging agent monomer allowing the formation of a poly(amino acid) backbone having 100% imaging agent conjugation if desired. However, the present method also permits the degree of conjugation to be controlled by copolymerizing the N-carboxyanhydride of the amino acid-imaging agent monomer with one or more unconjugated monomers, i.e. N-carboxyanhydrides of the same or of other amino acids. Various imaging agents may be employed, and new hybrid random, block, and mixed copolymers may be prepared.

Polyglutamates are well known to be highly biocompatible, biodegradable and multifunctional polymers, which have been already used as building blocks in polymer drug conjugates and polymeric micelles. Those systems have been applied to various medical applications ranging from therapy to molecular imaging. Furthermore a polyglutamic acid (PGA) paclitaxel conjugate has already entered clinical studies (Opaxio™ PGA-PTX conjugate currently in phase III of Clinical trials).In this context, a synthetic pathway to a plethora functional polyglutamates (homopolymers, block-co-polymers, tribocks) with well-defined structure, adjustable molecular weight (Mw) and low dispersity (D=Mw / Mn<1.2) applying the ring opening polymerization (ROP) of N-carboxyanhydrides (NCA) has been developed. Additionally, the acid moieties of the polyglutamates can be activated with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium (DMTMM) and various functionalities can be easily introduced by “post-polymerization modification” yielding a set orthogonal reactive attachment sides. The reactive moieties, such as azides, maleimides, thiols, akynes (linear or cyclic) offer the opportunity of specific conjugation of the drugs, targeting moieties or markers. Besides introducing reactive groups the functionalization strategy was also used for PEGylation of PGA reducing charge induced interactions and therefore pharmacological properties, such as blood circulation time may be adjusted.In summary, a tool kit of various polyglutamates has been developed enabling the synthesis of a variety of polymer drug conjugates or polymer based imaging agents. The functional polymeric precursors developed will allow us to functionalize and therefore adjust the polymer properties to a desired application.

Disclosed is a method of preparing an amino acid ester of maytansinol by reacting maytansinol with an N-carboxyanhydride of an amino acid (NCA) in the presence of a drying agent. Also disclosed is an improved method of preparing an amino acid ester of maytansinol in which a nucleophile is added to the reaction mixture after completion of the reaction between maytansinol and an N-carboxyanhydride of an amino acid.

A process for preparing N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanine N-carboxyanhydride of the following formula (I), is to react N-[1 -(S)-ethyoxy carbonyl-3-phenylpropyl]-L-alanine with XCOOR, wherein X is halogen atom, R is C1-C6 alkyl, to obtain a N-alkoxycarbonyl compound, then reacting with an acyl group activation reagent, finally contact with water. The compound of formula (I) is a key intermediate of ACE inhibitors. The preparation process has the advantages such as low toxicity, low hazard and easy operation etc.

The invention discloses a zein and glycopolypeptide grafted copolymer and a preparation method and application thereof. The preparation method comprises the steps that firstly, inherent amidogens of zein macromolecules are utilized to trigger an N-carboxyanhydride monomer containing azide functional groups for ring opening polymerization, azide-containing side-group polypeptide modified zein is obtained, and galactose is grafted to a polypeptide chain segment side group so as to obtain the zein and glycopolypeptide grafted copolymer. The zein and glycopolypeptide grafted copolymer prepared by means of the preparation method can be used for preparing a corresponding electrospun fibrous membrane serving as a liver cell scaffold material by adopting an electrospinning technique. The main raw material used for the zein and glycopolypeptide grafted copolymer belongs to a natural vegetable protein, a grafted glycopolypeptide chain segment is of a chemical structure similar to a glycoprotein in a living body, and therefore the prepared zein and glycopolypeptide grafted copolymer and the electrospun membrane scaffold material thereof have very good biocompatibility and bionic characteristics.