专利号:US-11667658-B2 优先权日:2021-06-30 标 题:Chemical synthesis of the organoarsenical antibiotic arsinothricin 发明人:ROSEN BARRY P; YOSHINAGA MASAFUMI; WNUK STANISLAW F; HOWLADER MD ABU HASAN; SUZOL SK MD SAZZAD HOSSAIN 权利人:ROSEN BARRY P; YOSHINAGA MASAFUMI; WNUK STANISLAW F; HOWLADER MD ABU HASAN; SUZOL SK MD SAZZAD HOSSAIN; THE FLORIDA INTERNATIONAL UNIV BOARD OF TRUSTEES 摘要:The subject invention provides methods for the chemical synthesis of racemic arsinothricin (D,L-AST), the novel organoarsenical antibiotic. One is by condensation of the 2-chloroethyl(methyl)arsinic acid with acetamidomalonate, and the second involves reduction of the N-acetyl-protected derivative of hydroxyarsinothricin (AST-OH) and subsequent methylation of the resulting sodium salt of trivalent arsenic intermediate with methyl iodide. The enzyme AST N-acetyltransferase (ArsN1) was utilized to purify L-AST from racemic AST. This expedient chemical synthesis of AST provides a source of this novel antibiotic for future drug development.
专利号:US-6683189-B1 优先权日:1996-02-26 标 题 :Method for the synthesis of pyrrole and imidazole carboxamides on a solid support 发明人:DERVAN PETER B; BAIRD ELDON 权利人:CALIFORNIA INST OF TECHN 摘要:The present invention describes a novel method for the solid phase synthesis of polyamides containing imidazole and pyrrole carboxamides. The polyamides are prepared on a solid support from aromatic carboxylic acids and aromatic amines with high stepwise coupling yields (>99%), providing milligram quantities of highly pure polyamides. The present invention also describes the synthesis of analogs of the natural products Netropsin and Distamycin A, two antiviral antibiotics. The present invention also describes a novel method for the solid phase synthesis of imidazole and pyrrole carboxamide polyamide-oligonucleotide conjugates. This methodology will greatly increase both the complexity and quantity of minor-groove binding polyamides and minor-groove binding polyamide-oligonucleotide conjugates which can be synthesized and tested.
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:WO-9002605-A1 优先权日:1988-09-02 标题:An apparatus and a method for the synthesis of peptides 发明人:MELDAL MORTEN; HOLM ARNE; BUCHARDT OLE 权利人:MELDAL MORTEN; HOLM ARNE; BUCHARDT OLE 摘要:An apparatus for use in chemical synthesis, especially peptide synthesis, comprises a synthesis chamber unit having a multiplicity of synthesis chambers, each of which has a liquid inlet and a liquid outlet, means for introducing liquid into the individual synthesis chambers and means for simultaneous removal of liquid via the liquid outlets of the synthesis chambers by regulation of the fluid pressure difference between the liquid inlets and the liquid outlets. A method for peptide synthesis using such an apparatus comprises the provision in each of the synthesis chambers of a solid-phase support material having a first, at least N-protected amino acid coupled thereto, after which a liquid deprotection reagent is introduced into the synthesis chambers. Following deprotection, the deprotection reagent is removed, after which a second, at least N-protected amino acid is introduced into each synthesis chamber in order to couple the first and second amino acids. Third, fourth, etc. amino acids may be coupled analogously. Complete removal of the deprotection reagent from the synthesis chambers and the support material can be ensured by incorporating a stable, intensely coloured dye, e.g., azorubin, in the deprotection reagent. The apparatus and the method make possible the parallel synthesis of a large number of peptides, e.g. peptides having overlapping amino acid sequences and constituting part of a longer peptide chain. The apparatus can be adapted to manual, semi-automatic or fully automatic performance of the various steps in the synthesis procedure.
专利号:US-4753985-A 优先权日:1981-10-07 标题 :Synthesis of organic compounds using deformable gel in porous rigid support 发明人:ROSEVEAR ALAN; SHEPPARD ROBERT C 权利人:ATOMIC ENERGY AUTHORITY UK 摘要:The present invention relates to the synthesis of chemical compounds and more particularly to the synthesis of organic compounds, for example, peptides and oligonucleotides. n The invention provides a composite material for use in the synthesis of organic compounds comprising a support material and, supported on the support material, an organic compound synthesizing substance. n It is preferred that the organic compound synthesizing substance is a gel (e.g. a dimethylacrylamide co-polymer gel). n The invention also provides a method for preparing a composite material for use in the synthesis of organic compounds and a method for the synthesis of organic compounds.
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.
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