Computationally Designed Cyclic Peptides Derived from an Antibody Loop Increase Breadth of Binding for Influenza Variants.
Computationally Designed Cyclic Peptides Derived from an Antibody Loop Increase Breadth of Binding for Influenza Variants.
复制标题
DOI：
10.1016/j.str.2020.04.005
复制
发表时间：
2020-10-06
期刊：
影响因子：
--
通讯作者：
Crowe JE Jr
中科院分区：
文献类型：
--
作者：
Sevy AM;Gilchuk IM;Brown BP;Bozhanova NG;Nargi R;Jensen M;Meiler J;Crowe JE Jr
流感血凝素 (HA) 糖蛋白是许多广泛中和抗体的靶标。然而，流感病毒可以通过与结合表位重叠的HA高变区的突变来快速逃避抗体识别。我们假设，通过设计肽来模拟抗体环，我们可以通过减少与介导逃逸的 HA 上高变残基的接触来增强与 HA 抗原变体的结合广度。我们设计了模拟抗流感广泛中和抗体 C05 的重链互补决定区 3 (CDRH3) 的环肽，并表明这些肽以 < 100 nM 的亲和力与 HA 分子结合，与全长亲本 C05 IgG 相当。此外，这些肽通过消除高变抗原区和抗体 CDRH1 环之间的冲突，表现出对流感 H4 和 H7 亚型的识别广度增加。这种方法可用于生成针对多种靶标的抗体衍生肽。塞维等人。开发了一种使用计算设计从抗体环创建环肽的方法。这些肽对季节性流感变异体具有广泛的结合活性，代表了肽发现的新策略。
The influenza hemagglutinin (HA) glycoprotein is the target of many broadly neutralizing antibodies. However, influenza viruses can rapidly escape antibody recognition by mutation of hypervariable regions of HA that overlap with the binding epitope. We hypothesized that by designing peptides to mimic antibody loops, we could enhance breadth of binding to HA antigenic variants by reducing contact with hypervariable residues on HA that mediate escape. We designed cyclic peptides that mimic the heavy chain complementarity-determining region 3 (CDRH3) of anti-influenza broadly neutralizing antibody C05 and show that these peptides bound to HA molecules with < 100 nM affinity, comparable to that of the full-length parental C05 IgG. In addition, these peptides exhibited increased breadth of recognition to influenza H4 and H7 subtypes by eliminating clashes between the hypervariable antigenic regions and the antibody CDRH1 loop. This approach can be used to generate antibody-derived peptides against a wide variety of targets. Sevy et al. have developed a method for creating cyclic peptides from antibody loops using computational design. These peptides have broad binding activity against seasonal influenza variants and represents a new strategy for peptide discovery.
登录
查看更多内容
影响因子：
64.8
作者：
Bhardwaj, Gaurav;Mulligan, Vikram Khipple;Bahl, Christopher D.;Gilmore, Jason M.;Harvey, Peta J.;Cheneval, Olivier;Buchko, Garry W.;Pulavarti, Surya V. S. R. K.;Kaas, Quentin;Eletsky, Alexander;Huang, Po-Ssu;Johnsen, William A.;Greisen, Per Jr;Rocklin, Gabriel J.;Song, Yifan;Linsky, Thomas W.;Watkins, Andrew;Rettie, Stephen A.;Xu, Xianzhong;Carter, Lauren P.;Bonneau, Richard;Olson, James M.;Coutsias, Evangelos;Correnti, Colin E.;Szyperski, Thomas;Craik, David J.;Baker, David
通讯作者：
Baker, David
影响因子：
2.9
作者：
Kaufmann, Kristian W.;Lemmon, Gordon H.;DeLuca, Samuel L.;Sheehan, Jonathan H.;Meiler, Jens
通讯作者：
Meiler, Jens
影响因子：
16.6
作者：
Crook ZR;Sevilla GP;Friend D;Brusniak MY;Bandaranayake AD;Clarke M;Gewe M;Mhyre AJ;Baker D;Strong RK;Bradley P;Olson JM
通讯作者：
Olson JM
影响因子：
5.4
作者：
Krause, Jens C.;Tsibane, Tshidi;Crowe, James E., Jr.
通讯作者：
Crowe, James E., Jr.
DOI：
10.1034/j.1399-3011.1999.00052.x
发表时间：
1999-05-01
期刊：
JOURNAL OF PEPTIDE RESEARCH
影响因子：
--
作者：
Bogdanowich-Knipp, SJ;Chakrabarti, S;Siahaan, TJ
通讯作者：
Siahaan, TJ