Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
The Symmetric Tetravalent Sulfhydryl-Specific Linker NATBA Facilitates a Combinatorial “Tool Kit” Strategy for Phage Display-Based Selection of Functionalized Bicyclic Peptides
ACS Omega ( IF 3.7 ) Pub Date : 2018-10-01 00:00:00 , DOI: 10.1021/acsomega.8b01814 Christoph Ernst 1 , Julia Sindlinger 2 , Dirk Schwarzer 2 , Pierre Koch 1 , Frank M. Boeckler 1, 3
ACS Omega ( IF 3.7 ) Pub Date : 2018-10-01 00:00:00 , DOI: 10.1021/acsomega.8b01814 Christoph Ernst 1 , Julia Sindlinger 2 , Dirk Schwarzer 2 , Pierre Koch 1 , Frank M. Boeckler 1, 3
Affiliation
|
The rigid conformation of constrained bicyclic peptides provides a number of advantages over larger protein-based ligands, including better chemical stability, enhanced tissue penetration, and a wider field of possible applications. Selective chemical modification strategies are able to extend the scope of applications not only in a therapeutic manner but also for the development of novel tools for protein capturing, bioimaging, and targeted drug delivery. Herein, we report the synthesis of an adamantane-based, symmetrical, tetravalent, sulfhydryl-specific peptide linker. We have developed an in vitro two-step modification strategy that allows the generation of differently functionalized bicyclic peptides. This “tool kit” strategy was applied to cyclize and functionalize a phage-encoded peptide library bearing the sequence CX6CX6C. After phage display against a model target, isolated peptides show strong consensus sequences, indicating target-specific binding. The newly developed symmetric tetravalent linker opens new avenues for the combinatorial selection and functionalization of bicyclic peptide ligands with affinity to virtually any target.
中文翻译：
对称的四价巯基特异性连接子NATBA促进了基于噬菌体展示的功能化双环肽选择的组合“工具包”策略
与较大的基于蛋白质的配体相比，受约束的双环肽的刚性构象具有许多优势，包括更好的化学稳定性，增强的组织渗透性和可能的应用范围。选择性化学修饰策略不仅能够以治疗方式扩展应用范围，而且还能够开发用于蛋白质捕获，生物成像和靶向药物递送的新型工具。在本文中，我们报告了基于金刚烷，对称，四价，巯基特异性肽接头的合成。我们已经开发了一种体外两步修饰策略，该策略允许生成功能不同的双环肽。该“工具包”策略用于环化和功能化带有CX序列的噬菌体编码肽库6 CX 6 C.在针对模型靶标的噬菌体展示后，分离的肽显示强共有序列，表明靶标特异性结合。新开发的对称四价连接子为双环肽配体的组合选择和功能化开辟了新途径，而该双环肽配体实际上对任何靶标都具有亲和力。
更新日期：2018-10-01
中文翻译：
对称的四价巯基特异性连接子NATBA促进了基于噬菌体展示的功能化双环肽选择的组合“工具包”策略
与较大的基于蛋白质的配体相比，受约束的双环肽的刚性构象具有许多优势，包括更好的化学稳定性，增强的组织渗透性和可能的应用范围。选择性化学修饰策略不仅能够以治疗方式扩展应用范围，而且还能够开发用于蛋白质捕获，生物成像和靶向药物递送的新型工具。在本文中，我们报告了基于金刚烷，对称，四价，巯基特异性肽接头的合成。我们已经开发了一种体外两步修饰策略，该策略允许生成功能不同的双环肽。该“工具包”策略用于环化和功能化带有CX序列的噬菌体编码肽库6 CX 6 C.在针对模型靶标的噬菌体展示后，分离的肽显示强共有序列，表明靶标特异性结合。新开发的对称四价连接子为双环肽配体的组合选择和功能化开辟了新途径，而该双环肽配体实际上对任何靶标都具有亲和力。
京公网安备 11010802027423号