Transcript Effect of Highly Fluorinated Amino Acids on Secondary Structure

Department of Chemistry
Seminar Announcement
Date/Time/Venue
Title/Speaker
27 Jan (Thu)
11am – 12nn
Effect of Highly Fluorinated Amino Acids
on Secondary Structure Stability
@ S8 Level 3
Executive
Classroom
Assoc Professor Richard Ping Cheng
National Taiwan University, Taiwan
Host : Assoc Prof Tan Choon Hong
About the Speaker
Assoc Professor Richard Ping Cheng obtained his B.S. degree in
chemistry from National Taiwan University in 1992. He then
continued his graduate studies with Barbara Imperiali and Harry
Gray at the California Institute of Technology and obtained his Ph.D.
degree in 1998. He carried out his postdoctoral research as an NIH
postdoctoral fellow at University of Pennsylvania School of Medicine
with William DeGrado (1998-2002) and DuPont Central Research &
Development with Mark Scialdone (1998 - 1999). He started his
independent career as the Jere Solo Assistant Professor of Medicinal and Organic
Chemistry at the State University of New York at Buffalo in 2002. In 2008, he moved to
the Department of Chemistry, National Taiwan University, as an Associate Professor.
His research interests include the synthesis, characteristics, and application of nonnatural amino acids.
Abstract
Highly fluorinated amino acids have been used to stabilize helical proteins, with limited
studies on sheet-containing proteins. Here we will present the effect of these highly
fluorinated amino acids on two protein secondary structures: alpha-helix and beta-sheet.
Furthermore, we will present a three-step chemoenzymatic stereoselective gram-scale
synthesis of fluorinated leucines. We will also show the effect of introducing fluorines on the
hydrophobicity of the amino acids. The helix propensity was measured using Ala-based
peptides, whereas the effect on beta-sheet stability was measured using protein G B1
domain (GB1). Various amino acids were studied including 5,5,5,5’,5’,5’-hexafluroleucine,
5,5,5’,5’-tetrafluoroleucine, pentafluorophenylalanine, leucine, phenylalanine, and alanine.
The peptides and proteins were synthesized by solid phase peptide synthesis. The
hydrophobicity of the amino acids were measured by thin layer chromatography under
neutral and acidic conditions. The Rf values were used to derive the logarithm of the
partition coefficient (logP) as a gauge for hydrophobicity. The circular dichroism spectra of
the Ala-based peptides were used to derive the helix propensity. Thermal denaturation of
GB1 derivatives were monitored by circular dichroism spectroscopy and used to explore the
effect on sheet stability. In general, complete fluorination of the methyl or phenyl groups
resulted in increase in hydrophobicity; partial fluorination of these groups led to decrease in
hydrophobicity. Helix propensity decreased significantly upon fluorination. In contrast, sheet
stability increased upon introducing the fluorines. Therefore, highly fluorinated amino acids
may be more suitable for stabilizing beta-sheets in sheet-containing proteins compared to
helical proteins.
All are Welcome