119th General Meeting of the KCS

Type Oral Presentation
Area Bioconjugation
Room No. 403호
Time THU 09:10-:
Code BIO.O-2
Subject Structural and Mechanistic Insights into Development of Chemical Tools to Control Individual and Inter-Related Pathological Features in Alzheimer’s Disease
Authors 이혁진, 임미희1,*
UNIST 생명과학연구부, Korea
1UNIST 자연과학부/화학과, Korea
Abstract To elucidate the involvement of individual and inter-related pathological factors [i.e., amyloid-β (Aβ), metals, and oxidative stress] in the pathogenesis of Alzheimer’s disease (AD), chemical tools have been developed. Characteristics required for such tool construction, however, have not been clearly identified; thus, the optimization of available tools or new design has been limited. In this presentation, we will present key structural properties and mechanisms that can determine tools’ regulatory reactivities with multiple pathogenic features found in AD. A series of small molecules was built up through rational structural selection and variations onto the framework of a tool useful for in vitro and in vivo metal–Aβ investigation. Variations include: (i) location and number of an Aβ interacting moiety; (ii) metal binding site; and (iii) denticity and structural flexibility. Detailed biochemical, biophysical, and computational studies were able to provide a foundation of how to originate molecular formulas to devise chemical tools capable of controlling the reactivities of various pathological components through distinct mechanisms. Overall, our multidisciplinary investigation illustrates that a structure-mechanism-based strategy can assist in significantly advancing the rational tool invention for such a complicated brain disease.
E-mail hyuckjin@unist.ac.kr