CONVENIENT TOTAL SYNTHESIS OF A 4-HELIX TASP MOLECULE BY CHEMOSELECTIVE LIGATION

CONVENIENT TOTAL SYNTHESIS OF A 4-HELIX TASP MOLECULE BY CHEMOSELECTIVE LIGATION
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DOI:
10.1021/ja00069a027
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发表时间:
1993-08-11
影响因子:
15
通讯作者:
KENT, SBH
KENT, SBH
中科院分区:
化学1区
文献类型:
--
作者:
DAWSON, PE;KENT, SBH

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制备复杂肽的化学选择性连接方法已用于简单、方便地合成模板组装的合成蛋白 (TASP) 分子。易于制备的未保护形式的合成前螺旋肽-αCOSH与同样处于未保护形式的合成(BrAc)4模板分子的反应在水溶液中快速进行,以高产率得到均匀产物。所得 4-螺旋 TASP 简单纯化至均质,并通过离子喷雾质谱法确定共价结构 [obs MW 6647.1 +/- 2.8 D;计算值 6645.6(单一同位素),6649.9(平均同位素组成)]。所得大分子的构象通过圆二色性(CD)测定并且是高度螺旋的。未受保护的肽的化学选择性连接代表了合成 TASP 分子的通用方法。
The chemoselective ligation approach to the preparation of complex peptides has been used in a simple, convenient synthesis of a template-assembled synthetic protein (TASP) molecule. Reaction of a readily prepared synthetic pro-helical peptide-alphaCOSH, in unprotected form, with a synthetic (BrAc)4 template molecule, also in unprotected form, proceeded rapidly in aqueous solution to give a uniform product in high yield. The resulting 4-helix TASP was simply purified to homogeneity, and the covalent structure was defined by ion-spray mass spectrometry [obs MW 6647.1 +/- 2.8 D; calc 6645.6 (monoisotopic), 6649.9 (average isotope composition)]. The conformation of the resulting macromolecule was determined by circular dichroism (CD) and was highly helical. The chemoselective ligation of unprotected peptides represents a general approach to the synthesis of TASP molecules.