专利号:WO-2024165450-A1 优先权日:2023-02-09 标题:Method of chemical synthesis of single-chain antibody fragments and products thereby obtained 发明人:FIGINI MARIANGELA; LUISON ELENA 权利人:GLYTECH INC; FIGINI MARIANGELA 摘要:A new method is disclosed for the protein full-chemical synthesis of single-chain antibody fragments (scFv); the obtained products are structurally close and functionally equivalent to their biological counterpart, being however, advantageously free of impurities and more reproducible in properties. The method includes the general steps of: (a) separately synthetizing sub-sequences (peptide fragments) (b) sequentially assembling the sub-sequences obtained in step (a) in the order as they appear in the target scFv amino acid sequence, and (c) performing oxidative folding of the assembled whole peptide molecule obtained in step (b) and dialyzing the resulting product in a buffer.
专利号:US-8404804-B2 优先权日:2007-08-28 标 题 :Methods and intermediates for chemical synthesis of polypeptides and proteins 发明人:DONG ZHENG XIN; EYNON JOHN S 权利人:DONG ZHENG XIN; EYNON JOHN S; IPSEN PHARMA SAS 摘要:The present invention relates to methods and intermediates for chemical synthesis of polypeptides and proteins, and more particularly to methods and intermediates for chemically ligating a peptide fragment containing N-terminal N-methyl-cysteine (SEQ ID NO: 1) with another peptide fragment having C-terminal thioester to generate a β-(methylamino)-thioester intermediate that spontaneously rearranges to form an amide bond. Furthermore, the invention relates to methods of converting N-methyl-thiazolidine to N-methyl-cysteine (SEQ ID NO: 1) of polypeptides and proteins. The invention also relates to methods of synthesizing peptide-thioester from peptide-acid fluoride.
专利号:US-2010204449-A1 优先权日:2007-09-04 标 题 :Methods and intermediates for chemical synthesis of polypeptides and proteins 发明人:DONG ZHENG XIN; KIM SUN H 权利人:DONG ZHENG XIN; KIM SUN H 摘要:The present invention relates to methods and intermediates for chemical synthesis of polypeptides and proteins, and more particularly to methods and intermediates for chemically ligating a peptide fragment containing N-terminal β-methyl-cysteine (SEQ ID NO: 1) with another peptide fragment having C-terminal thioester to generate a β-amino-thioester intermediate that spontaneously rearranges to form an amide bond. The invention also relates to methods of synthesizing β-methyl-cysteine (SEQ ID NO: 1) and its protected forms. Furthermore, the invention relates to converting a β-methyl-thiazolidine residue to a β-methyl-cysteine (SEQ ID NO: 1) residue of polypeptides and proteins.
专利号:US-2020190135-A1 优先权日:2016-11-16 标题 :Lasso structures and their synthesis 发明人:BODE JEFFREY; SAITO FUMITO 权利人:CHROMACON AG 摘要:A method for the synthesis of a molecular lasso structure in which a linear moiety is covalently attached to a cyclic moiety and with its free end is partially threaded through the orifice formed by the cyclic moiety, including the following steps: 1) provision of a cyclic and a first linear structural element and establishing conditions in which the first linear structural element is threaded through the orifice of the cyclic moiety; 2) covalently attaching a stopper element to one terminal end of the linear structural element; 3) separating unthreaded from threaded molecular assemblies by chemical or physical separation; and 4) reacting the threaded molecular assemblies with a second linear structural element so that it is covalently attached to the first linear structural element at its end opposite to the end where the stopper is attached, and so that the second linear structural element is covalently attached to the cyclic moiety.
专利号:US-9850275-B2 优先权日:2013-09-11 标 题 :Photolabile linker for the solid-phase synthesis of hydrazides and pyranopyrazoles 发明人:NIELSEN THOMAS E; QVORTRUP KATRINE 权利人:UNIV DANMARKS TEKNISKE 摘要:The photolabile hydrazine linker of the present invention is based on the o-nitro-veratryl group, which is capable of releasing hydrazide derivatives upon UV irradiation. The linker allows for a new solid-phase peptide synthesis (SPPS) strategy which is fully orthogonal to the most commonly used protecting groups and chemical methods in SPPS and shows excellent compatibility with peptide composition, notably the 20 naturally occurring α-amino acid residues (even in their side-chain protected form) are accepted in the C-terminal of the peptide hydrazides. Furthermore, the linker unit can be applied to synthesize combinatorial libraries of biological interesting heterocyclic compounds, such as pyranopyrazoles.
专利号:US-2022233673-A1 优先权日:2019-06-04 标 题:METHODS OF PRODUCING SHIGA TOXIN B-SUBUNIT (STxB) MONOMERS AND OLIGOMERS, AND USES THEREOF 发明人:BILLET ANNE; SCHMIDT FRÉDÉRIC; JOHANNES LUDGER; SERVENT DENIS; MOURIER GILLES; TARTOUR ÉRIC; KAY MICHAEL; FULCHER JAMES M 权利人:INST CURIE; CENTRE NAT RECH SCIENT; INST NAT SANTE RECH MED; COMMISSARIAT A LENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES CEA; APHP ASSIST PUBLIQUE HOPITAUX DE PARIS; UNIV PARIS; UNIV OF UTAH RESEARCH FOUDATION; UNIV UTAH RES FOUND 摘要:A method of producing a monomer of a Shiga toxin B-subunit (STxB) protein or of a variant thereof by peptide chemical synthesis, as well as to a method of producing a pentamer of the STxB protein or of the variant thereof. The methods are particularly advantageous as they overcome major issues typically observed in peptide chemical synthesis, including solubility and purity issues.
[参考文献]: Daniel J Capon, Et Al. Flexible Antibodies With Nonprotein Hinges. Proc Jpn Acad Ser B Phys Biol Sci. 2011;87(9):603-16. [参考文献]: Paul W R Harris, Et Al. Chemical Synthesis Of A Polypeptide Backbone Derived From The Primary Sequence Of The Cancer Protein Ny-Eso-1 Enabled By Kinetically Controlled Ligation And Pseudoprolines. Biopolymers. 2015 Mar;104(2):116-27.
合成参考文献
摘要:Malins, L. R.; Payne, R. J., Science of Synthesis Knowledge Updates, (2021) 3, 195.