2019
DOI: 10.1002/anie.201813954
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An Intrinsic Hydrophobicity Scale for Amino Acids and Its Application to Fluorinated Compounds

Abstract: More than 100 hydrophobicity scales have been introduced, with each being based on ad istinct condensedphase approach.However,acomparison of the hydrophobicity values gained from different techniques,a nd their relative ranking,isnot straightforward, as the interactions between the environment and the amino acid are unique to each method. Here,weovercome this limitation by studying the properties of amino acids in the clean-room environment of the gas phase.In the gas phase,e ntropic contributions from the hyd… Show more

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Cited by 34 publications
(39 citation statements)
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References 38 publications
(77 reference statements)
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“…Furthermore, replacing the tyrosine hydroxyl group with an electron withdrawing fluorine, by means of substitution with 4-fluoro-L-phenylalaine, caused significant impairment of agonist activity, both decreasing calcium signaling and significantly decreasing ␤-arrestin recruitment (AYPGK-F(4-fluoro)-NH 2 , calcium EC 50 ϭ ND; ␤-arr-1, 25.2 Ϯ 6.5%; ␤-arr-2, 41.3 Ϯ 5.9%). The results of these two substitutions suggest that altering the polarity, while maintaining aromaticity, in position 6 reduces efficacy (33). Because decreasing hydrophobicity did not increase PAR4-AP activity, we next investigated alterations that increase stericity and hydrophobicity.…”
Section: Effect Of Additional Substitutions In Position 6 On Par4-apmmentioning
confidence: 99%
“…Furthermore, replacing the tyrosine hydroxyl group with an electron withdrawing fluorine, by means of substitution with 4-fluoro-L-phenylalaine, caused significant impairment of agonist activity, both decreasing calcium signaling and significantly decreasing ␤-arrestin recruitment (AYPGK-F(4-fluoro)-NH 2 , calcium EC 50 ϭ ND; ␤-arr-1, 25.2 Ϯ 6.5%; ␤-arr-2, 41.3 Ϯ 5.9%). The results of these two substitutions suggest that altering the polarity, while maintaining aromaticity, in position 6 reduces efficacy (33). Because decreasing hydrophobicity did not increase PAR4-AP activity, we next investigated alterations that increase stericity and hydrophobicity.…”
Section: Effect Of Additional Substitutions In Position 6 On Par4-apmmentioning
confidence: 99%
“…This is not surprising, since significant differences between both scales exist as they are based on different principles [26] . To overcome this limitation, our group was recently involved in the development of a universal hydrophobicity scale based on clustering of amino acids in the gas phase revealing a unique behavior of fluorinated Phe variants by a decrease in hydrophobicity compared to Phe [27] …”
Section: Resultsmentioning
confidence: 99%
“…[26] To overcome this limitation, our group was recently involved in the development of a universal hydrophobicity scale based on clustering of amino acids in the gas phase revealing a unique behavior of fluorinated Phe variants by a decrease in hydrophobicity compared to Phe. [27] Besides hydrophobicity, πÀ π interactions have been proposed to play a significant role during amyloid formation in general but several conflicting reports about their importance exist. [21,28] These interactions can be defined as a sum of the interplay between aromatic side chains involving hydrophobic, van der Waals, and also electrostatic forces.…”
Section: Design Of Halogenated Nfgail Variantsmentioning
confidence: 99%
“…Moreover, they modulate the properties of peptides and proteins [5][6][7], influencing aspects such as protein folding, protein-protein interactions, ribosomal translation, lipophilicity, acidity/basicity, optimal pH, stability, thermal stability, and therapeutic properties [8][9][10]. This extends to metabolic properties of membrane permeability and reactivity [11][12][13][14]. The effect of peptide structure and stability has been found to depend on the position and number of fluorine atoms within the amino acid chains [15][16][17].…”
Section: Introductionmentioning
confidence: 99%