公开(公告)号：US20140378668A1

公开(公告)日：2014-12-25

申请号：US14315214

申请日：2014-06-25

Applicant: The Scripps Research Institute

Inventor： Carlos F. Barbas, III ,  Hitoshi Ban ,  Julia Gavrilyuk

IPC: A61K47/48 ,  A61K31/4196 ,  A61K31/47 ,  A61K31/439

CPC classification number: A61K31/4196 ,  A61K31/439 ,  A61K31/47 ,  A61K47/6891 ,  C07D249/00 ,  C07D249/12 ,  C07D403/14 ,  C07D417/10

Abstract: A new and versatile class of cyclic diazodicarboxamides that reacts efficiently and selectively with phenols and the phenolic side chain of tyrosine through an Ene-like reaction is reported. This mild aqueous tyrosine ligation reaction works over a broad pH range and expands the repertoire of aqueous chemistries available for small molecule, peptide, and protein modification. The tyrosine ligation reactions are shown to be compatible with the labeling of native enzymes and antibodies in buffered aqueous solution. This reaction provides a novel synthetic approach to bispecific antibodies. This reaction will find broad utility in peptide and protein chemistry and in the chemistry of phenol-containing compounds.

Abstract translation: 报道了一种新的多功能一类环状重氮二酰胺，通过Ene样反应有效和选择性地与苯酚和酪氨酸的侧链反应。 这种温和的水性酪氨酸连接反应在广泛的pH范围内起作用，并扩展了可用于小分子，肽和蛋白质修饰的水性化学成分。 显示酪氨酸连接反应与缓冲水溶液中天然酶和抗体的标记相容。 该反应为双特异性抗体提供了新的合成方法。 该反应将在肽和蛋白质化学和含酚化合物的化学中发现广泛的用途。