Strategy for Conjugating Oligopeptides to Mesoporous Silica Nanoparticles Using Diazirine-Based Heterobifunctional Linkers.

Strategy for Conjugating Oligopeptides to Mesoporous Silica Nanoparticles Using Diazirine-Based Heterobifunctional Linkers.
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使用基于二氮丙啶的异双功能连接体将寡肽缀合至介孔二氧化硅纳米颗粒的策略。

DOI:
10.3390/nano12040608
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发表时间:
2022-02-11
期刊:
Nanomaterials (Basel, Switzerland)
影响因子:
--
通讯作者:
Knutson BL
Knutson BL
中科院分区:
其他
文献类型:
--
作者:
Khan MA;Ghanim RW;Kiser MR;Moradipour M;Rogers DT;Littleton JM;Bradley LH;Lynn BC;Rankin SE;Knutson BL

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将寡肽附着到具有足够大的孔以装载生物分子的介孔二氧化硅的成功策略应该利用孔的高表面积来提供可接近的保护性环境。一个两步寡肽功能化策略,在这里检查使用基于二氮丙啶异双功能接头。合成了平均孔径约为8 nm、比表面积约为730 m2/g的介孔二氧化硅纳米粒子(MSNPs)并进行了胺官能化。四肽Gly-Gly-Gly-Gly(GGGG)和Arg-Ser-Ser-Val(RSSV)以及由四个拷贝的RSSV(4 RSSV)组成的肽通过异双功能连接体磺基琥珀酰亚胺基6-(4,4 ′-azipentanamido)己酸酯(磺基-NHS-LC-二氮丙啶或SNLD)通过其N-末端共价连接至颗粒表面上的胺基。SNLD由胺反应性NHS酯基团和UV活化的二氮杂环丙烯基团组成,可精确控制连接步骤的顺序。用异硫氰酸荧光素标记的RSSV(RSSV-FITC)检测RSSV的附着效率。TGA分析显示4G、RSSV和4 RSSV的相似效率(分别为0.29、0.31和0.26 mol肽/mol胺),表明肽缀合的可推广方法。这里开发的用于肽与MSNP缀合的技术提供了它们在孔中的附着,并且可以转化为选择性的基于肽的分离和浓缩来自水性工艺和废物流的治疗剂。
Successful strategies for the attachment of oligopeptides to mesoporous silica with pores large enough to load biomolecules should utilize the high surface area of pores to provide an accessible, protective environment. A two-step oligopeptide functionalization strategy is examined here using diazirine-based heterobifunctional linkers. Mesoporous silica nanoparticles (MSNPs) with average pore diameter of ~8 nm and surface area of ~730 m2/g were synthesized and amine-functionalized. Tetrapeptides Gly-Gly-Gly-Gly (GGGG) and Arg-Ser-Ser-Val (RSSV), and a peptide comprised of four copies of RSSV (4RSSV), were covalently attached via their N-terminus to the amine groups on the particle surface by a heterobifunctional linker, sulfo-succinimidyl 6-(4,4′-azipentanamido)hexanoate (sulfo-NHS-LC-diazirine, or SNLD). SNLD consists of an amine-reactive NHS ester group and UV-activable diazirine group, providing precise control over the sequence of attachment steps. Attachment efficiency of RSSV was measured using fluorescein isothiocyanate (FITC)-tagged RSSV (RSSV-FITC). TGA analysis shows similar efficiency (0.29, 0.31 and 0.26 mol peptide/mol amine, respectively) for 4G, RSSV and 4RSSV, suggesting a generalizable method of peptide conjugation. The technique developed here for the conjugation of peptides to MSNPs provides for their attachment in pores and can be translated to selective peptide-based separation and concentration of therapeutics from aqueous process and waste streams.
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