Jeonghun Lee

Stimuli-Responsive Conformational Conversion of Peptide Gatekeepers for Controlled Release of Guests from Mesoporous Silica Nanocontainers

The use of peptides as gatekeepers for payloads of mesoporous silica nanoparticles would allow triggering the release of guests by various biological stimuli. We investigated the effect of peptide conformation on their gatekeeping capability by employing two model peptides with a turn or a random structure. The conformation-dependent gatekeeping properties provided an opportunity to utilize the conformational conversion of peptides as a valuable motif for stimuli-responsive gatekeepers. Based on that investigation, we demonstrated that Fmoc-CGGC-SS-Si, which exhibited a zero-release property without any stimuli due to a turn-like conformation induced by the intramolecular disulfide bond, can be triggered to release guests by converting its conformation to a random structure, induced by reduction of the disulfide bond upon addition of glutathione. We further demonstrated that the conformational conversion of Fmoc-CGGC by Zn(II) ion can also be utilized as a triggering motif.

Self-organization of amide dendrons with focal dipeptide units†

Dendron–dipeptide conjugates were synthesized to investigate their self-assembly characteristics not only in the aqueous phase but also in organic media. In the aqueous phase, the self-organized structure of 2G-PhePhe and 2G-GlyGly was influenced predominantly by the self-assembly characteristics of the amide dendron unit to exhibit vesicular structures. For 1G-PhePhe and 1G-GlyGly, however, the role of the focal dipeptide unit became important to show donut-like assemblies and rod-like structures, respectively. In HFIP/H2O (1 : 100 v/v), 2G-PhePhe and 1G-PhePhe exhibited donut-like structures, while 2G-GlyGly and 1G-GlyGly formed rod-like structures. The secondary structures of the dendron–peptide conjugates were remarkably influenced by the dendron unit. The circular dichroism (CD) spectra showed that 1G-PhePhe in H2O adopted the β-sheet structure. On increasing the generation of the dendron unit, on the other hand, 2G-PhePhe did not adopt the β-sheet structure but exhibited random structures. In addition, the curvature of the assembled structure of the dendron–peptide conjugates was affected by the dendron unit. In organic media such as toluene, all the dendron–dipeptide conjugates formed fibrous structures which could induce thermoreversible gel formation. Therefore, the modulation of the dendritic moiety and the focal peptide unit provided an opportunity to produce diverse self-organized structures in various conditions.

Fluorescent Dendron–Cyclodextrin Nanotubes with Surface Peptide Spacer as a Recyclable Sensory Platform

Nanotube sensory platform: Dendron-cyclodextrin nanotubes with a surface coumarin unit attached by a GH dipeptide spacer were constructed by a combination of molecular recognition and self-assembly. These unique fluorescent nanotubes can serve as a recyclable metal ion sensory platform with high selectivity and sensitivity (see scheme).

Nanotubular Assembly of Amide Dendron and Cucurbiturils

Self-assembly provides a unique way of facile control of sophisticated nanoachitectures to create supramolecular functional materials. Among many different types of building blocks, dendrons and dendrimers have recently been of great interest in a variety of scientific fields due to their unique assembly characteristics and functional performances. In particular, amide dendrons exhibit myriad supramolecular architectures such as nanoribbons, nanofibers, vesicles, and nanotubes. The supramolecular structure induced by self-organization of the amide dendrons can be controlled not only by the environmental conditions of selfassembly but also by tuning the focal functionality of amide dendrons. In particular, a cooperative self-assembly of an amide dendron and cyclodextrins (CDs) was reported to produce an unprecedented nanotubular architecture. The in-situ inclusion of the focal pyrene unit of the amide dendron into the cavity of CDs induced a supramolecular transformation from vesicular organization of the amide dendron to dendron–CD nanotubes, the surface of which is covered with CDs. Therefore, the surface functionality of the nanotube could be controlled efficiently by using C-6 modified CDs in the self-assembly to provide diverse dendron–CD nanotubes. In addition, this type of new nanotubes showed unique sensory capability. Thus, we reasoned that cucurbit[n]urils (CB[n]s) would provide an opportunity for the focal pyrene moiety of the amide dendron to be included in the cavity of CBs and subsequent supramolecular transformation from the vesicular assembly of the amide dendron to the nanotubular architecture through self-assembly of the dendron–CB complex. CB[n]s have a macrocyclic structure consisting of 5–10 glycoluril repeating units and have a cavity in the middle of a pumpkin-like structure. For example, CB[8] has a cavity with internal and portal diameters of about 8.8 and 6.9 , respectively. In addition, the cavity volume of CB[8] is about 479 . Due to the structural characteristics of CB[8], inclusion complexes with a wide range of guest molecules such as Phe-Gly-Gly (FGG) and 1-adamantanamine (1-ad) have been reported. Herein, we report the formation of dendron–CB nanotubes with CB units on the surface (2G-Py-CB-NT) by supramolecular transformation of the vesicle of the amide dendron induced by in-situ inclusion complex formation between the focal pyrene moiety of the amide dendron (2GPy) and the cavity of CBs, as shown in Figure 1. In addition,

Self-assembled dendron nanotubes with a surface peptide–fluorophore conjugate as a sensory vehicle

We report a facile approach to construct the hierarchically self-assembled dendron–cyclodextrin (CD) nanotubes with a dansyl fluorophore connected to the surface of the tube via a Gly-Gly-His (GGH) tripeptide spacer unit (Den-dans-GGH-CD-NTs) through a molecular recognition process of CDs and an amide dendron with the focal pyrene moiety. Den-dans-GGH-CD-NTs were utilized as a sensory platform for Cu(II) which can selectively bind to the GGH unit on the nanotube. Upon addition of Cu(II) into the tubular solution of Den-dans-GGH-CD-NTs, the fluorescence quenching of the dansyl fluorophore was observed due to photo-induced electron transfer to copper ions. A quantitative analysis showed that the detection limit for copper(II) ions was 148 nM. Furthermore, the Den-dans-GGH-CD-NT platform can be reused by abstraction of Cu(II) from the GGH unit with retaining the sensory capability.

Stimuli-responsive α-helical peptide gatekeepers for mesoporous silica nanocarriers

Among the numerous gatekeepers, peptides have attracted much interest due to their specific targeting, cell penetrating, endo-/lysosomal escaping, and enzymatic degrading capabilities. Recently, we developed peptide gatekeepers with turn structures that were triggered to release via stimuli-responsive conformational conversion. In this report, to extend the utilization of stimuli-responsive peptide gatekeepers on the surface of MSNs, we prepared α-helical peptide gatekeepers with a capability for stimuli-responsive conformational conversion on the surface of mesoporous silica nanoparticles. The stimuli-responsive α-helical peptide gatekeepers controlled the release of entrapped drugs triggered by GSH addition and consequential conformational conversion. Furthermore, the nanoparticles efficiently disrupted the liposome membranes. Therefore, stimuli-responsive α-helical peptide gatekeepers would be useful for the construction of mesoporous delivery vehicles with enhanced therapeutic efficacy via membrane disruption.

Nanotubular self-organization of amide dendrons with focal β-sheet forming peptide units

To develop rational design principles for a self-organized structure using dendron-peptide conjugates, a β-sheet forming short peptide (VVLL) was introduced to the focal point of a second-generation amide dendron (2G-VVLL) and its self-organization characteristics were investigated. 2G-VVLL self-organized into a nanotubular structure in the aqueous phase. The twisted β-sheet structure of the focal peptide unit was essential for the construction of the nanotubular structure. The design principle could be applied to another dendron-peptide conjugate (2G-AAVV). These findings are expected to assist in the construction of novel precisely controlled nanoarchitectures using amide dendrons with focal peptide units.

Analytical Study to Check Safety of Folding-type Staircase in High Speed Rolling Stock

2004년 프랑스 알스톰과 국내 철도차량 제작사에서 제작 한 KTX의 승강문 시스템은 저상 승강장에서 승객이 탑승 가능하도록 제작이 되어 있다. 광역 전철 역사는 차량의 바 닥 높이와 승강장의 높이가 일치하는 고상 승강장의 형태를 갖추고 있고, 도시간 원거리를 운행하는 일반 객차 및 고속 열차 역사는 고상 승강장 형태를 갖는다. 승강장의 높이는 차량의 승강대 및 발판의 형태에 영향을 주게 되며, 승객의 승하차 편의성과 밀접한 관계가 있다. 국내 승강장의 높이에 대한 규정은 도시철도건설규칙 및 철도건설규칙에 따라 레일 상면으로부터 고상 승강장은 1,135mm, 저상 승강장은 500mm이다.[1] KTX의 승강문 스텝은 ‘Fig. 1’과 같이 저상 승강장에서 차 량의 바닥면까지 3개의 발판을 이용하여 탑승을 하며, 차량 내부에 고정되어 있는 2개의 발판과 차량 외부로 개폐되는 1개의 접이식 발판으로 구성되어 있다. KTX에 적용되어 있는 접이식 발판은 승강문 시스템의 유 럽 규격인 EN14752에 따라 제작이 되어 있으나 차량 외부 로 돌출되는 발판의 폭이 200mm여서 국내 20세에서 60세 성인 남성의 평균 발 크기인 253mm[2]에 미치지 못하고 있 다. 걸을 때 신체 하중은 대부분 발 뒤축에 걸리므로 탑승 시 발판에 안전하게 신체 하중을 실을 수가 없다. 탑승객이 많을 때나 급히 탑승을 할 때에는 전도나 미끄러짐의 위험 이 있으며, 특히 비나 눈이 내려 발판이 젖어 있을 때에는 위험도는 더욱 높아지게 된다. KTX 승강문 발판에 대한 강 도 해석을 최근 신정훈 등[3]이 수행하였고 본 논문에서는 Abstract The KTX, running in Korea but imported from Alstom Co. in France, has folding type staircases complying with European standard EN 4752. However, when operating, the step size is only 200mm, while the Korean standard step size is 253mm, a standard reflecting the average value of persons aged 20~60. From the aspect of kinesiology, the current step size can cause falls or slips during embarking and disembarking of passengers because body load is mostly focused on the heel and the current step is much more narrow than the standard size. Thus, we have performed an analytical study to check the safety of folding type staircases on the KTX after re-design.