Abstract
Structural modifications of peptides and proteins using fluorinated amino acids provide the opportunity to modulate their biophysical and pharmaceutical properties. Systematic investigations based on model systems that mimic natural protein-protein interaction domains, such as the coiled-coil folding motif, can provide valuable insights into the behaviour of side chain fluorinated amino acids in natural protein environments. Here, we report the incorporation of hexafluoroleucine and two trifluorovaline stereoisomers at two different hydrophobic core positions of an established parallel heterodimeric coiled-coil model system to evaluate the impact of these substitutions on coiled-coil structure and stability. All of the resulting fluorinated peptides form stable α-helical bundles, and the single substitution of leucine with hexafluoroleucine leads to an increase in thermal stability.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 32-35 |
| Number of pages | 4 |
| Journal | Journal of Fluorine Chemistry |
| Volume | 175 |
| DOIs | |
| State | Published - Jul 1 2015 |
| Externally published | Yes |
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Keywords
- CD spectroscopy
- Fluorinated amino acids
- Hexafluoroleucine
- Trifluorovaline
- α-Helical coiled coil
ASJC Scopus subject areas
- Biochemistry
- Environmental Chemistry
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry
Cite this
Effects of single substitutions with hexafluoroleucine and trifluorovaline on the hydrophobic core formation of a heterodimeric coiled coil. / Huhmann, Susanne; Nyakatura, Elisabeth K.; Erdbrink, Holger; Gerling, Ulla I.M.; Czekelius, Constantin; Koksch, Beate.
In: Journal of Fluorine Chemistry, Vol. 175, 01.07.2015, p. 32-35.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of single substitutions with hexafluoroleucine and trifluorovaline on the hydrophobic core formation of a heterodimeric coiled coil
AU - Huhmann, Susanne
AU - Nyakatura, Elisabeth K.
AU - Erdbrink, Holger
AU - Gerling, Ulla I.M.
AU - Czekelius, Constantin
AU - Koksch, Beate
PY - 2015/7/1
Y1 - 2015/7/1
N2 - Structural modifications of peptides and proteins using fluorinated amino acids provide the opportunity to modulate their biophysical and pharmaceutical properties. Systematic investigations based on model systems that mimic natural protein-protein interaction domains, such as the coiled-coil folding motif, can provide valuable insights into the behaviour of side chain fluorinated amino acids in natural protein environments. Here, we report the incorporation of hexafluoroleucine and two trifluorovaline stereoisomers at two different hydrophobic core positions of an established parallel heterodimeric coiled-coil model system to evaluate the impact of these substitutions on coiled-coil structure and stability. All of the resulting fluorinated peptides form stable α-helical bundles, and the single substitution of leucine with hexafluoroleucine leads to an increase in thermal stability.
AB - Structural modifications of peptides and proteins using fluorinated amino acids provide the opportunity to modulate their biophysical and pharmaceutical properties. Systematic investigations based on model systems that mimic natural protein-protein interaction domains, such as the coiled-coil folding motif, can provide valuable insights into the behaviour of side chain fluorinated amino acids in natural protein environments. Here, we report the incorporation of hexafluoroleucine and two trifluorovaline stereoisomers at two different hydrophobic core positions of an established parallel heterodimeric coiled-coil model system to evaluate the impact of these substitutions on coiled-coil structure and stability. All of the resulting fluorinated peptides form stable α-helical bundles, and the single substitution of leucine with hexafluoroleucine leads to an increase in thermal stability.
KW - CD spectroscopy
KW - Fluorinated amino acids
KW - Hexafluoroleucine
KW - Trifluorovaline
KW - α-Helical coiled coil
UR - http://www.scopus.com/inward/record.url?scp=84926220510&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84926220510&partnerID=8YFLogxK
U2 - 10.1016/j.jfluchem.2015.03.003
DO - 10.1016/j.jfluchem.2015.03.003
M3 - Article
AN - SCOPUS:84926220510
VL - 175
SP - 32
EP - 35
JO - Journal of Fluorine Chemistry
JF - Journal of Fluorine Chemistry
SN - 0022-1139
ER -