三(2-氰乙基)膦置于盐酸体系中,化学反应 2.0H,以88%的收率获得产物三(2-羰基乙基)磷盐酸盐 参考文献:Selective Reduction Of Disulfides By Tris(2-Carboxyethyl)Phosphine 标题:Selective Reduction Of Disulfides By Tris(2-Carboxyethyl)Phosphine 摘要:Tris(2-Carboxyethyl)Phosphine (Tcep) Reduces Disulfides Rapidly And Completely In Water At Ph 4.5. It Preferentially Reduces More Strained Disulfides,In Accordance With The Usual Mechanism Postulated For Reduction Of Disulfides By Phosphines In Water. The Reagent Can Be Synthesized Conveniently In Large Quantities By Acidic Hydrolysis Of The Commercially Available Tris(2-Cyanoethyl)Phosphine. DOI:10.1021/jo00008A014
专利号:US-12421534-B2 优先权日:2021-11-10 标 题 :Engineered enzymes and method for the synthesis of diverse tyrosine analogs 发明人:ALMHJELL PATRICK J; ARNOLD FRANCES H 权利人:CALIFORNIA INST OF TECHN 摘要:Provided herein is an engineered tryptophan synthase β-subunit (TrpB) that catalyzes the synthesis of tyrosine, tyrosine analogs, or salts thereof. Also provided herein are methods for preparing tyrosine, tyrosine analogs, or a salt thereof using the engineered TrpB described herein.
专利号:US-7589170-B1 优先权日:1998-09-25 标题 :Synthesis of cyclic peptides 发明人:SMYTHE MARK LESLIE; MEUTERMANS WIM DENIS FRANS; BOURNE GREGORY THOMAS; MCGEARY ROSS PETER 权利人:UNIV QUEENSLAND 摘要:This invention relates to methods for preparing cyclic peptides and peptidomimetic compounds in solution and bound to solid supports, and to cyclic peptide or peptidomimetic libraries for use in drug screening programs. In particular, the invention relates to a generic strategy for synthesis of cyclic peptides or peptidomimetics that enables the efficient synthesis under mild conditions of a wide variety of desired compounds. Two approaches were evaluated for their improvements in solution and solid phase synthesis of small cyclic peptides: positioning reversible N-amide substituents in the sequence; and applying native ligation chemistry in an intramolecular sense. Systematic investigation of the effects of preorganising peptides prior to cyclisation by using peptide cyclisation auxiliaries, and developing new linkers and peptide cyclisation auxiliaries to aid cyclic peptide synthesis gives surprising improvements in both yields and purity of products compared to the prior art methods. The combination of these technologies provides a powerful generic approach for the solution and solid phase synthesis of small cyclic peptides. The ring contraction and N-amide substitution technology of the invention provide improved methods for the synthesis of cyclic peptides and peptidomimetics. When used in conjunction with linker strategies, this combination provides solid-phase avenues to cyclic peptides and peptidomimetics.
专利号:US-2023235372-A1 优先权日:2020-06-12 标题:Ab-initio, template-independent synthesis of nucleic acids using thermostable enzymes 发明人:RANDRIANJATOVO-GBALOU IRINA; SAID AHMED; RAHIER RENAUD 权利人:SYNHELIX 摘要:The invention relates to the field of nucleic acid synthesis or sequencing, more specifically to methods for ab-initio synthesis of nucleic acids, comprising contacting a nucleotide with a free 3′-hydroxyl group, with at least one nucleoside triphosphate, or a combination of nucleoside triphosphates, in the presence of an archaeal DNA primase or a functionally active fragment and/or variant thereof, thereby covalently binding said nucleoside triphosphate to the free 3′-hydroxyl group of the nucleotide. It also relates to isolated functionally active fragments of archaeal DNA primases which are capable of both ab-initio single-stranded nucleic acid synthesis activity and template-independent terminal nucleotidyl transferase activity.
专利号:WO-2023012709-A1 优先权日:2021-08-05 标 题 :An improved process for fmoc synthesis of semaglutide 发明人:LOBO LESTER JOHN; CHANDRAKESAN MURALIDHARAN; DOSHI CHETAN; CHANADAK SHAILESH LALCHAND; YADAV NANDLAL GOPAL; MOHE NIKHIL UMESH; VISHWANATHAN KODANDARAMAN 权利人:USV PRIVATE LTD 摘要:The present invention relates to an improved process for the synthesis of glucagon-like-peptide-1 (GLP-1) and its analogs by using combination of solid and solution phase synthesis of Fmoc protected amino acids in a sequential manner, optionally incorporating Boc protected dipeptide for unnatural amino acid in the Sequence of GLP-1, cleaving GLP-1 sequence from the resin followed by purification; attaching side-chain to the desired amino acid in the solution phase to synthesize desired GLP-1 analog, purifying it to Semaglutide. Temperature gradient is applied during initial coupling of amino acids to facilitate completion of difficult coupling reactions.
专利号:US-2023313255-A1 优先权日:2020-07-15 标题:Massively Parallel Enzymatic Synthesis of Polynucleotides 发明人:HORGAN ADRIAN; LACHAIZE HENRI; VERARDO DOMIANO; GODRON XAVIER 权利人:DNA SCRIPT 摘要:The invention is directed to methods and compositions for inkjet assisted synthesis of a plurality of polynucleotides at reaction sites on a substrate using template-free polymerases, such as, terminal deoxynucleotidyl transferases (TdTs). Compositions of the invention include formulations of synthesis reagents for inkjet delivery including, but not limited to, TdT coupling reaction buffers and 3′-O-protected dNTP monomers.
专利号:US-2023331778-A1 优先权日:2020-08-31 标 题 :An improved process for fmoc synthesis of etelcalcetide 发明人:LOBO LESTER JOHN; CHANDRAKESAN MURALIDHARAN; DOSHI CHETAN; CHANADAK SHAILESH LALCHAND; YADAV NANDLAL GOPAL; MOHE NIKHIL UMESH; VISHWANATHAN KODANDARAMAN; CHAVRE PRAFUL SHAMRAO 权利人:USV PRIVATE LTD 摘要:The present invention relates to an improved process for the synthesis of Etelcalcetide and its analogs by solid phase synthesis of Fmoc protected amino acids in a sequential manner, followed by acetylation of terminal D-cys and cleavage of peptide from solid support. The crude heptapeptide thus obtained is reduced using Tris(2-carboxyethyl) phosphine hydrochloride, purified and oxidized with L-cysteine. The oxidized Etelcalcetide is purified and salt exchanged using a one-step reverse phase chromatography process. The purified Etelcalcetide hydrochloride is then precipitated using organic solvents, concentrated and lyophilized to purity of greater than 99.0%.
[参考文献]: Dieguez-Acuña Fj, Et Al. Inhibition Of Nf-Kappab-Dna Binding By Mercuric Ion: Utility Of The Non-Thiol Reductant, Tris(2-Carboxyethyl)Phosphine Hydrochloride (Tcep), On Detection Of Impaired Nf-Kappab-Dna Binding By Thiol-Directed Agents. Toxicol In Vitro. 2000 Feb;14(1):7-16. [参考文献]: Duchardt F, Et Al. A Cell-Penetrating Peptide Derived From Human Lactoferrin With Conformation-Dependent Uptake Efficiency. J Biol Chem. 2009 Dec 25;284(52):36099-108. [参考文献]: Han Jc, Han Gy. A Procedure For Quantitative Determination Of Tris(2-Carboxyethyl)Phosphine, An Odorless Reducing Agent More Stable And Effective Than Dithiothreitol. Anal Biochem. 1994;220(1):5-10. [参考文献]: Sequeira Ma, Et Al. Modulating Amyloid Fibrillation In A Minimalist Model Peptide By Intermolecular Disulfide Chemical Reduction. Phys Chem Chem Phys. 2019 Jun 5;21(22):11916-11923. [参考文献]: Wu R, Et Al. Effects Of Small Molecules On Dna Adsorption By Gold Nanoparticles And A Case Study Of Tris(2-Carboxyethyl)Phosphine (Tcep). Langmuir. 2019 Oct 15;35(41):13461-13468.
合成参考文献
参考文献:10.1038/ncomms1409 摘要:Li T, Yang Y, Canessa CM. Outlines of the pore in open and closed conformations describe the gating mechanism of ASIC1. Nat Commun. 2011 Jul 19;2():399. doi: 10.1038/ncomms1409.