논문 (학술지)
Tailoring Hydrophobic Interactions between Probes and Amyloid-beta Peptides for Fluorescent Monitoring of Amyloid-beta Aggregation
| 등록번호 | RPMS-2018-0190689394 | SCI 구분
?
※구분 : SCI(SCIE포함), 비SCI |
SCI |
|---|---|---|---|
| 저자명 (주·공동저자) | Kim Sonam; Lee Hyuck Jin; Nam Eunju; Jeong Donghyun; Cho Jaeheung; Lim Mi Hee; You Youngmin | ||
| 논문구분 | 국외전문학술지 | 학술지명 | ACS OMEGA |
| ISSN | 2470-1343 | 학술지 출판일자 | 2018-05-11 |
| 학술지 볼륨번호 | 3 | 논문페이지 | 5141 ~ 5154 |
| 학술지 임팩트팩터 | 0.0 | 기여율 | 20 % |
| DOI | 10.1021/acsomega.8b00286 | ||
| 초록 | Despite their unique advantages, the full potential of molecular probes for fluorescent monitoring of amyloid-β (Aβ) aggregates has not been fully exploited. This limited utility stems from the lack of knowledge about the hydrophobic interactions between the molecules of Aβ probes, as well as those between the probe and the Aβ aggregate. Herein, we report the first mechanistic study, which firmly establishes a structure−signaling relationship of fluorescent Aβ probes. We synthesized a series of five fluorescent Aβ probes based on an archetypal donor−acceptor−donor scaffold (denoted as SN1−SN5). The arylamino donor moieties were systematically varied to identify molecular factors that could influence the interactions between molecules of each probe and that could influence their fluorescence outcomes in conditions mimicking the biological milieu. Our probes displayed different responses to aggregates of Aβ, Aβ40 and Aβ42, two major isoforms found in Alzheimer’s disease: SN2, having pyrrolidine donors, showed noticeable ratiometric fluorescence responses (Δν = 797 cm−1) to the Aβ40 and Aβ42 samples that contained oligomeric species, whereas SN4, having N-methylpiperazine donors, produced significant fluorescence turn-on signaling in response to Aβ aggregates, including oligomers, protofibrils, and fibrils (with turn-on ratios of 14 and 10 for Aβ42 and Aβ40, respectively). Mechanistic investigations were carried out by performing field-emission scanning electron microscopy, X-ray crystallography, UV−vis absorption spectroscopy, and steady-state and transient photoluminescence spectroscopy experiments. The studies revealed that the SN probes underwent preassembly prior to interacting with the Aβ species and that the preassembled structures depended profoundly on the subtle differences between the amino moieties of the different probes. Importantly, the studies demonstrated that the mode of fluorescence signaling (i.e., ratiometric response versus turn-on response) was primarily governed by stacking geometries within the probe preassemblies. Specifically, ratiometric fluorescence responses were observed for probes capable of forming J-assembly, whereas fluorescence turn-on responses were obtained for probes incapable of forming J-aggregates. This finding provides an important guideline to follow in future efforts at developing fluorescent probes for Aβ aggregation. We also conclude, on the basis of our study, that the rational design of such fluorescent probes should consider interactions between the probe molecules, as well as those between Aβ peptides and the probe molecule. | ||
연구개발성과 등록 또는 활용에 대한 문의는 논문 연구개발성과 담당자를 통해 문의하시기 바랍니다.
[문의] 한국과학기술정보연구원 Tel : 042)716-7066, https://curation.kisti.re.kr/
- NTIS 관련 이용문의는 NTIS 콜센터(042-869-1115)로 문의하시기 바랍니다.
NTIS의 논문 정보는 국가연구개발사업 수행을 통해 발생된 성과로, 조사분석 등을 통해 입력된 정보를 수집 및 제공하고 있어, 출판사 또는 논문 정보 제공 사이트(Scienceon, RISS 등)에서 일괄 제공하는 논문 정보와 차이가 있을 수 있습니다.