专利号:US-7301006-B2 优先权日:2002-07-16 标 题 :Methods and materials for the synthesis of modified peptides 发明人:YOUNG TRAVIS G; KIESSLING LAURA L 权利人:WISCONSIN ALUMNI RES FOUND 摘要:Methods and protected amino acids useful as building blocks (protected monomers) for the synthesis of peptides and proteins that are selectively modified at one or more side-chain hydroxyl groups. Azide-bearing protecting groups allow the selective deprotection of side-chain hydroxyl groups of amino acids after synthesis of a peptide. Reaction conditions for removal of the azide-bearing protecting group can be selected which are substantially orthogonal to those that will remove α-amino protecting groups typically employed in peptide synthesis, such that hydroxyl groups protected with the azide-bearing protecting group remain protected during synthesis of the peptide chain. Various protecting groups which are readily available can be used for protecting potentially reactive side chain groups of amino acids in the peptide or protein to be modified. Preferred side-chain protecting groups are chemically distinguishable from the azide-bearing protecting group and substantially orthogonal reaction conditions can be selected such that side-chain protection of other amino acids is maintained when the azide-bearing protecting group is removed. The use of the azide-bearing protecting group of this invention for one or more hydroxy amino acids during peptide synthesis allows the selective unmasking of those azide-protected side-chain hydroxyl groups and selective modification of the hydroxyl groups that are selectively unmasked. The methods and materials herein are particularly used in synthesis of sulfated, phosphorylated and glycosylated peptides and proteins. Kits and methods of synthesizing a modified peptide or protein using the kits are also provided.
专利号:US-5374541-A 优先权日:1993-05-04 标 题 :Combined use of β-galactosidase and sialyltransferase coupled with in situ regeneration of CMP-sialic acid for one pot synthesis of oligosaccharides 发明人:WONG CHI-HUEY; GAETA FEDERICO C A 权利人:SCRIPPS RESEARCH INST; CYTEL CORP 摘要:A single reaction vessel process for the synthesis of a sialylated galactoside is disclosed. The synthesis utilizes a β-galactosidase to catalyze the reaction of a galactose-containing substrate and an acceptor to form a new galactosyl glycoside that is then sialylated using a cyclic multienzyme synthesis system to form CMP-sialic acid that sialylates the formed galactosyl glycoside in the presence of an α-sialyltransferase. The value of K m /V max for the formed galactosyl glycoside as a substrate for the α-sialyltransferase is less than one-third the K m /V max value for the galactose-containing substrate for that α-sialyltransferase.
专利号:US-6579725-B1 优先权日:1999-03-05 标题 :Linkers for synthesis of oligosaccharides on solid supports 发明人:SEEBERGER PETER H; ANDRADE RODRIGO B 权利人:MASSACHUSETTS INST TECHNOLOGY 摘要:The present invention relates to versatile linkers for tethering a molecule to a solid support, e.g., for tethering a monomer, oligomer or polymer to a solid support, which are stable to a wide range of reaction conditions, but can be cleaved under well-defined conditions, thereby liberating the molecule from the solid support. Preferably, the linkers are used to tether to the solid support unprotected, partially-protected or fully-protected monosaccharides or oligosaccharides, or unprotected, partially-protected or fully-protected glycoconjugates. The linkers of the present invention may be used to tether to solid supports building blocks useful in the assembly of libraries of other types of small molecules. The present invention also relates to a molecule or plurality of molecules tethered to the solid support via a linker or linkers of the present invention. The present invention also relates to processes for synthesizing molecules, e.g., monomers, oligomers or polymers, on a solid support, wherein a starting material in the synthesis of the molecule, intermediates in the synthesis of the molecule, and the molecule itself are tethered to the solid support during the process via one of the linkers of the present invention. In certain processes of the present invention, the molecule is liberated from the solid support by cleavage of the linker of the present invention.
专利号:US-5856143-A 优先权日:1993-05-14 标 题 :N-containing saccharides and method for the synthesis of N-containing saccharides from amino-deoxy-disaccharides and amino-deoxy-oligosaccharides 发明人:NILSSON KURT G I 权利人:BIOFLEXIN AB 摘要:Synthesis of an amino-disaccharide, amino-oligosaccharide or a derivative thereof, characterized in that a monosaccharide, a disaccharide, an oligosaccharide, a glycoside or a derivative thereof, in the presence of a glycosidase as catalyst, is reacted with an amino-deoxy-saccharide or a derivative thereof, and that the amino-saccharide is isolated from the product mixture directly or after chemical/enzymatic modification.
专利号:US-6846917-B2 优先权日:2001-01-23 标题:Solid- and solution-phase synthesis of heparin and other glycosaminoglycans 发明人:SEEBERGER PETER H; ORGUEIRA HERNAN; SCHELL PETER 权利人:MASSACHUSETTS INST TECHNOLOGY 摘要:Described is a modular, general synthetic strategy for the preparation in solution and on a solid support of heparin, heparin-like glycosaminoglycans, glycosaminoglycans and non-natural analogs of each of them. Additionally, the modular strategy provides the basis for the preparation of combinatorial libraries and parallel libraries of defined glycosaminoglycan oligosaccharides. The defined glycosaminoglycan structures may be used in high-throughput screening experiments to identify carbohydrate sequences that regulate a host of recognition and signal-transduction processes. The determination of specific sequences involved in receptor binding holds great promise for the development of molecular tools which will allow modulation of processes underlying viral entry, angiogenesis, kidney diseases and diseases of the central nervous system. Notably, the present invention enables the automated synthesis of glycosaminoglycans in much the same fashion that peptides and oligonucleotides are currently assembled.
专利号:WO-9508553-A1 优先权日:1993-09-22 标 题 :Synthesis of selectin ligands 发明人:NICOLAOU K C; BOCKOVICH NICHOLAS J; CARCANAGUE DANIEL R 权利人:SCRIPPS RESEARCH INST; NICOLAOU K C; BOCKOVICH NICHOLAS J; CARCANAGUE DANIEL R 摘要:The total synthesis of the naturally occurring sulfated Le?x and Lea¿ tetrasaccharides, trisaccharide analogs of sulfated Le?x and Lea¿, and multivalent Lex selectin ligands are described.
1: Liu JH, Tian YY, Zhao XY, Li YL, Lyu YN, Liu C, Lin ZZ, Wang ZJ, Zuo ZP, Wang ZB. [Research on mechanism of hypolipidemic effect of Massa Medicata Fermentata based on metabolomics]. Zhongguo Zhong Yao Za Zhi. 2024 Feb;49(3):770-778. Chinese. doi: 10.19540/j.cnki.cjcmm.20231019.401. 12(1):32. doi: 10.3390/pharmacy12010032. 3: Elsayed SI, El-Dahan MS, Girgis GNS. Pharmacodynamic Studies of Pravastatin Sodium Nanoemulsion Loaded Transdermal Patch for Treatment of Hyperlipidemia. AAPS PharmSciTech. 2024 Feb 8;25(2):34. doi: 10.1208/s12249-024-02746-5. 15(3):925. doi: 10.3390/pharmaceutics15030925. 5: Maehara Y, Oki E, Ota M, Harimoto N, Ando K, Nakanishi R, Kawazoe T, Fujimoto Y, Nonaka K, Kitao H, Iimori M, Makino K, Takechi T, Sagara T, Miyadera K, Matsuoka K, Tsukihara H, Kataoka Y, Wakasa T, Ochiiwa H, Kamahori Y, Tokunaga E, Saeki H, Yoshizumi T, Kakeji Y, Shirabe K, Baba H, Shimada M. Lineage of drug discovery research on fluorinated pyrimidines: chronicle of the achievements accomplished by Professor Setsuro Fujii. Int J Clin Oncol. 2023 May;28(5):613-624. doi: 10.1007/s10147-023-02326-w. Epub 2023 Mar 24.
合成参考文献
参考文献:10.1124/jpet.105.084830 摘要:Hirano M, Maeda K, Hayashi H, Kusuhara H, Sugiyama Y. Bile Salt Export Pump (BSEP/ABCB11) Can Transport a Nonbile Acid Substrate, Pravastatin. The Journal of Pharmacology and Experimental Therapeutics. 2005 Aug;314(2):876–82. doi: 10.1124/jpet.105.084830.