Dendrimer-Mediated Molecular Sieving on Avidin

IF 5.4 2区 化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biomacromolecules Pub Date : 2025-02-10 Epub Date: 2025-01-31 DOI:10.1021/acs.biomac.4c01696
Billy Deng , Stuart Alexander McNelles , Jingyu Sun , Joaquin Ortega , Alex Adronov
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Abstract

Decoration of proteins and enzymes with well-defined polymeric structures allows precise decoration of protein surfaces, enabling controlled modulation of activity. Here, the impact of dendronization on the interaction between avidin and biotin was investigated. A series of generation 3–7 bis­(2,2-hydroxymethyl)­propionic acid (bis-MPA) dendrons were coupled to either biotin or avidin to yield a library of dendronized avidin and biotin structures. The thermodynamics of binding each biotinylated generation to a library of avidin conjugates was probed with isothermal titration calorimetry (ITC). Dissociation constants of high-generation biotin-dendrons (G5 and G6) with higher-generation avidin-dendron conjugates (Av-G6) increased from ∼10–15 M (for the native structures) to ∼10–6 M, and binding was found to be weaker than that of the Avidin-HABA complex. Avidin-G5 and Avidin-G6 were highly size-selective for biotinylated ligands; both prevented the binding of aprotinin (6.9 kDa), bovine serum albumin (BSA), and PEG3400 while forming fractional complexes with smaller biotinylated dendrons.
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树突分子介导的亲和素分子筛选。
用定义明确的聚合物结构修饰蛋白质和酶,可以对蛋白质表面进行精确修饰,从而实现活性的可控调节。本文研究了树突化对亲和素与生物素相互作用的影响。将一系列3-7代双(2,2-羟甲基)丙酸(bis- mpa)树突偶联到生物素或亲和素上,得到了一个树突化的亲和素和生物素结构文库。用等温滴定量热法(ITC)研究了每一代生物素化产物与亲和素偶联物库结合的热力学。高代生物素-树突(G5和G6)与高代亲和素-树突偶联物(Av-G6)的解离常数从~ 10-15 M(天然结构)增加到~ 10-6 M,并且发现结合比亲和素- haba复合物弱。Avidin-G5和Avidin-G6对生物素化配体具有高度的尺寸选择性;两者都阻止了抑蛋白蛋白(6.9 kDa)、牛血清白蛋白(BSA)和PEG3400的结合,同时与较小的生物素化树梢形成了分式复合物。
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来源期刊
Biomacromolecules
Biomacromolecules 化学-高分子科学
CiteScore
10.60
自引率
4.80%
发文量
417
审稿时长
1.6 months
期刊介绍: Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.
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