High temperature SELMA: evolution of DNA-supported oligomannose clusters which are tightly recognized by HIV bnAb 2G12.
High temperature SELMA: evolution of DNA-supported oligomannose clusters which are tightly recognized by HIV bnAb 2G12.
复制标题
高温SELMA：由HIV BNAB 2G12紧紧识别的DNA支持的寡素糖簇的演变。
DOI：
10.1021/ja411212q
复制
发表时间：
2014-02-05
影响因子：
15
通讯作者：
Krauss IJ
中科院分区：
文献类型：
--
作者：
Temme JS;MacPherson IS;DeCourcey JF;Krauss IJ
SELMA（SELection with Modified Aptamers）是一种定向进化方法，其可用于开发DNA支持的碳水化合物簇，其中簇的几何形状被优化以用于被感兴趣的凝集素强识别。在此，我们报告了SELMA的修饰，其导致糖簇，其实现显著更强的靶标识别（100倍），具有显著更少的聚糖（2-3倍）。我们的SELMA的第一次应用产生了5-10个寡甘露糖聚糖的簇，其被具有中等亲和力（150-500 nM Kd）的广泛中和HIV抗体2G 12识别。在本手稿中，我们报告了仅含有3-4个聚糖的糖簇，其被2G 12识别，Kd低至1.7 nM。这些糖簇与HIV包膜蛋白gp 120一样被2G 12紧密识别，并且它们是第一个以占据2G 12上的结合位点所需的最小数量的Man 9单元（3-4）实现这种紧密识别的构建体。因此，它们作为可能引发针对HIV的广泛中和抗体的免疫原而引起极大兴趣。
SELMA (SELection with Modified Aptamers) is a directed evolution method which can be used to develop DNA-supported clusters of carbohydrates in which the geometry of clustering is optimized for strong recognition by a lectin of interest. Herein, we report a modification of SELMA which results in glycoclusters which achieve dramatically stronger target recognition (100-fold) with dramatically fewer glycans (2–3-fold). Our first applications of SELMA yielded clusters of 5–10 oligomannose glycans which were recognized by broadly neutralizing HIV antibody 2G12 with moderate affinities (150–500 nM Kd’s). In the present manuscript, we report glycoclusters containing just 3–4 glycans, which are recognized by 2G12 with Kd’s as low as 1.7 nM. These glycoclusters are recognized by 2G12 as tightly as is the HIV envelope protein gp120, and they are the first constructs to achieve this tight recognition with the minimal number of Man9units (3–4) necessary to occupy the binding sites on 2G12. They are thus of great interest as immunogens which might elicit broadly neutralizing antibodies against HIV.
登录
查看更多内容
影响因子：
4.9
作者：
Ciobanu, Mihai;Huang, Kuo-Ting;Winssinger, Nicolas
通讯作者：
Winssinger, Nicolas
DOI：
10.1073/pnas.1002717107
发表时间：
2010-10-05
影响因子：
11.1
作者：
Doores, Katie J.;Fulton, Zara;Davis, Benjamin G.
通讯作者：
Davis, Benjamin G.
影响因子：
5.4
作者：
Sanders, RW;Venturi, M;Moore, JP
通讯作者：
Moore, JP
影响因子：
2.9
作者：
Abdiche, Yasmina;Malashock, Dan;Pons, Jaurne
通讯作者：
Pons, Jaurne
影响因子：
4.7
作者：
Ni, JH;Song, HJ;Wang, LX
通讯作者：
Wang, LX