J Food Bioact

Journal of Food Bioactives, ISSN 2637-8752 print, 2637-8779 online

Journal website www.isnff-jfb.com

Review

Volume 4, Number , December 2018, pages 88-98

Role of hydrophobicity in food peptide functionality and bioactivity

Figure 1.

Role of hydrophobicity in several functionalities and health-related bioactivities of food protein-derived peptides.

Figure 2.

Enzymatic hydrolysis in producing hydrophobic peptides for stabilizing emulsions.

Figure 3.

Various applications of peptide self-assembly.

**Table 1.** Amino acid hydrophobicity scales
Amino acid	Symbol	Hydrophobicity Scale
Isoleucine	Ile (I)	4.50	1.38	0.88	4.80	0.31	−1.80
Valine	Val (V)	4.20	1.08	0.86	4.70	−0.07	−1.50
Leucine	Leu (L)	3.80	1.06	0.85	5.70	0.56	−1.80
Phenylalanine	Phe (F)	2.80	1.19	0.88	4.40	1.13	−2.50
Cysteine	Cys (C)	2.50	0.29	0.91	4.10	0.24	−1.00
Methionine	Met (M)	1.90	0.64	0.85	4.20	0.23	−1.30
Alanine	Ala (A)	1.80	0.62	0.74	0.20	−0.17	−0.50
Glycine	Gly (G)	−0.40	0.48	0.72	0.00	−0.01	0.00
Threonine	Thr (T)	−0.70	−0.05	0.70	−1.90	−0.14	−0.40
Serine	Ser (S)	−0.80	−0.18	0.66	−0.50	−0.13	0.30
Tryptophan	Trp (W)	−0.90	0.81	0.85	1.00	1.85	−3.40
Tyrosine	Tyr (Y)	−1.30	0.26	0.76	3.20	0.94	−2.30
Proline	Pro (P)	−1.60	0.12	0.64	−2.20	−0.45	0.00
Histidine	His (H)	−3.20	−0.40	0.78	0.50	−0.96	−0.50
Glutamic acid	Glu (E)	−3.50	−0.74	0.62	−1.80	−2.02	3.00
Glutamine	Gln (Q)	−3.50	−0.85	0.62	−2.80	−0.58	0.20
Aspartic acid	Asp (D)	−3.50	−0.90	0.62	−3.10	−1.23	3.00
Asparagine	Asn (N)	−3.50	−0.78	0.63	−0.50	−0.42	0.20
Lysine	Lys (K)	−3.90	−1.50	0.52	−3.10	−0.99	3.00
Arginine	Arg (R)	−4.50	−2.53	0.64	1.40	−0.81	3.00

Table 1. Amino acid hydrophobicity scales

Amino acid

Symbol

Hydrophobicity Scale

Kyte and Doolittle (1982)

Eisenberg et al. (1984)

Wolfenden et al. (1983)

Cornette et al. (1987)

Wimley and White (1996)

Hopp and Woods (1983)

Isoleucine

Ile (I)

4.50

1.38

0.88

4.80

0.31

−1.80

Valine

Val (V)

4.20

1.08

0.86

4.70

−0.07

−1.50

Leucine

Leu (L)

3.80

1.06

0.85

5.70

0.56

−1.80

Phenylalanine

Phe (F)

2.80

1.19

0.88

4.40

1.13

−2.50

Cysteine

Cys (C)

2.50

0.29

0.91

4.10

0.24

−1.00

Methionine

Met (M)

1.90

0.64

0.85

4.20

0.23

−1.30

Alanine

Ala (A)

1.80

0.62

0.74

0.20

−0.17

−0.50

Glycine

Gly (G)

−0.40

0.48

0.72

0.00

−0.01

0.00

Threonine

Thr (T)

−0.70

−0.05

0.70

−1.90

−0.14

−0.40

Serine

Ser (S)

−0.80

−0.18

0.66

−0.50

−0.13

0.30

Tryptophan

Trp (W)

−0.90

0.81

0.85

1.00

1.85

−3.40

Tyrosine

Tyr (Y)

−1.30

0.26

0.76

3.20

0.94

−2.30

Proline

Pro (P)

−1.60

0.12

0.64

−2.20

−0.45

0.00

Histidine

His (H)

−3.20

−0.40

0.78

0.50

−0.96

−0.50

Glutamic acid

Glu (E)

−3.50

−0.74

0.62

−1.80

−2.02

3.00

Glutamine

Gln (Q)

−3.50

−0.85

0.62

−2.80

−0.58

0.20

Aspartic acid

Asp (D)

−3.50

−0.90

0.62

−3.10

−1.23

3.00

Asparagine

Asn (N)

−3.50

−0.78

0.63

−0.50

−0.42

0.20

Lysine

Lys (K)

−3.90

−1.50

0.52

−3.10

−0.99

3.00

Arginine

Arg (R)

−4.50

−2.53

0.64

1.40

−0.81

3.00

**Table 2.** Bioinformatic tools for calculating the hydrophobicity of peptides
Bioinformatic tools	Platform provider	Website
Peptide 2.0	Peptide 2.0 Inc.	https://www.peptide2.com/N_peptide_hydrophobicity_hydrophilicity.php
Peptide property tool	Genescript	https://www.genscript.com/tools/peptide-property-calculator
Peptide analysing tool	ThermoFisher Scientific	https://www.thermofisher.com/ca/en/home/life-science/protein-biology/peptides-proteins/custom-peptide-synthesis-services/peptide-analyzing-tool.html
Peptide property calculator	Biosynthesis	https://www.biosyn.com/peptidepropertycalculator/peptidepropertycalculator.aspx
PepCalc.com	Innovagen	https://pepcalc.com/
Prot pi peptide tool	Prot pi	https://www.protpi.ch/Calculator/PeptideTool
Peptide property calculator	Northwestern University	http://biotools.nubic.northwestern.edu/proteincalc.html
PLATINUM	Laboratory of Biomolecular Modelling, Russian Academy of Sciences	https://model.nmr.ru/platinum/
Peptide Library Design and Calculator Tool	Millipore Sigma	https://www.sigmaaldrich.com/technical-documents/articles/biology/peptide-library-design-and-calculator-tool.html
GPMAW lite	Alphalyse Inc.	https://www.alphalyse.com/customer-support/gpmaw-lite-bioinformatics-tool/start-gpmaw-lite/
R-software	R Core Team	https://www.r-project.org/contributors.html

Table 2. Bioinformatic tools for calculating the hydrophobicity of peptides

Bioinformatic tools

Platform provider

Website

Peptide 2.0

Peptide 2.0 Inc.

https://www.peptide2.com/N_peptide_hydrophobicity_hydrophilicity.php

Peptide property tool

Genescript

https://www.genscript.com/tools/peptide-property-calculator

Peptide analysing tool

ThermoFisher Scientific

https://www.thermofisher.com/ca/en/home/life-science/protein-biology/peptides-proteins/custom-peptide-synthesis-services/peptide-analyzing-tool.html

Peptide property calculator

Biosynthesis

https://www.biosyn.com/peptidepropertycalculator/peptidepropertycalculator.aspx

PepCalc.com

Innovagen

https://pepcalc.com/

Prot pi peptide tool

Prot pi

https://www.protpi.ch/Calculator/PeptideTool

Peptide property calculator

Northwestern University

http://biotools.nubic.northwestern.edu/proteincalc.html

PLATINUM

Laboratory of Biomolecular Modelling, Russian Academy of Sciences

https://model.nmr.ru/platinum/

Peptide Library Design and Calculator Tool

Millipore Sigma

https://www.sigmaaldrich.com/technical-documents/articles/biology/peptide-library-design-and-calculator-tool.html

GPMAW lite

Alphalyse Inc.

https://www.alphalyse.com/customer-support/gpmaw-lite-bioinformatics-tool/start-gpmaw-lite/

R-software

R Core Team

https://www.r-project.org/contributors.html

**Table 3.** Food protein-derived bioactive peptides, with highlighted hydrophobic regions, and their respective bioactivities
Sequence	Bioactivity	Experimental analysis	Reference
Phe-Asp-Ser-Gly-Pro-Ala-Gly-Val-Leu	Antioxidant capacity	In vitro analysis with human lung fibroblasts	Mendis et al. (2005)
Asn-Gly-Pro-Leu-Gln-Ala-Gly-Gln-Pro-Gly-Glu-Arg
Gly-Val-Ser-Asn-Ala-Ala-Val-Val-Ala-Gly-Gly-His	Antioxidant capacity	In vitro and ex vivo analysis on mouse fibroblasts	Coda et al. (2012)
Asp-Ala-Gln-Glu-Phe-Lys-Arg
Tyr-Ala	Antioxidant capacity	In vitro analysis using standard methods involving ABTS, DPPH and superoxide anion	Tang et al. (2010)
Glu-Gln-Arg-Pro-Arg	Anticancer activity	In vitro analysis in diverse normal and cancer cell cultures	Kannana et al. (2010)
Gly-Gly-Arg-Lys-Gln-Gly-Gln-His-Gln-Gln-Glu-Glu	Immunostimulating	In vitro and in vivo analysis in cell cultures and mice models	Gusa and Tani (2009)
Val-Ile-Lys	Anti-inflammatory activity	In vitro analysis in murine macrophage cell lines	(Dia et al (2014)
Tyr-Val-Pro-Gly-Pro	Anticancer activity	In vitro analysis on prostate cancer cells	Wu et al. (2018)
Ile-Pro	DPP-IV inhibition	In vitro analysis	Hatanaka et al. (2012)
Leu-Pro
Lys-Ala	DPP-IV inhibition	In vitro analysis	Gallego et al. (2014)
Ala-Ala-Ala-Thr-Pro
Arg-Trp	Antimicrobial activity	Increase in antimicrobial activity and hemolysis of red blood cells with increasing peptide chain length	Liu et al. (2007)
Arg-Trp-Arg-Trp
Arg-Trp-Arg-Trp-Arg-Trp
Arg-Trp-Arg-Trp-Arg-Trp-Arg-Trp
Arg-Trp-Arg-Trp-Arg-Trp-Arg-Trp-Arg-Trp
Val-Gln-Trp-Arg-Ile-Arg-Val-Ala-Val-Ile-Arg-Lys	Antimicrobial activity	60 mg/kg dose shown to be as effective as vancomycin in rats with Staphylococcus aureus	Wu et al. (2014)
Val-Leu-Leu-Val-Thr-Leu-Thr-Arg-Leu-His-Gln-Arg-Gly-Val-Ile-Tyr-Arg-Lys-Trp-Arg-His-Phe-Ser-Gly-Arg-Lys-Tyr-Arg	Antimicrobial activity	Antimicrobial studies with Escherichia coli DH5α, Bacillus subtilis AZ54, Staphylococcus aureus ATCC 6538 P and Pseudomonas aeruginosa strains	Pane et al. (2017)
Glu-Lys-Glu-Arg-Glu-Arg-Gln	ACE inhibition	Oral administration to spontaneously hypertensive rats (SHR) at a dose of 10 mg/kg body weight	Katayama et al. (2008)
Lys-Arg-Gln-Lys-Tyr-Asp-Ile
Lys-Arg-Val-Ile-Gln-Try	ACE inhibition	Oral administration to SHR at a dose of 10 mg/kg body weight	Muguruma et al. (2009)
Arg-Pro-Arg	ACE inhibition	Oral administration to SHR at a dose of 1 mg/kg body weight	Escudero et al. (2012)
Lys-Ala-Pro-Val-Ala
Pro-Thr-Pro-Val-Pro

Table 3. Food protein-derived bioactive peptides, with highlighted hydrophobic regions, and their respective bioactivities

Sequence

Bioactivity

Experimental analysis

Reference

Phe-Asp-Ser-Gly-Pro-Ala-Gly-Val-Leu

Antioxidant capacity

In vitro analysis with human lung fibroblasts

Mendis et al. (2005)

Asn-Gly-Pro-Leu-Gln-Ala-Gly-Gln-Pro-Gly-Glu-Arg

Gly-Val-Ser-Asn-Ala-Ala-Val-Val-Ala-Gly-Gly-His

Antioxidant capacity

In vitro and ex vivo analysis on mouse fibroblasts

Coda et al. (2012)

Asp-Ala-Gln-Glu-Phe-Lys-Arg

Tyr-Ala

Antioxidant capacity

In vitro analysis using standard methods involving ABTS, DPPH and superoxide anion

Tang et al. (2010)

Glu-Gln-Arg-Pro-Arg

Anticancer activity

In vitro analysis in diverse normal and cancer cell cultures

Kannana et al. (2010)

Gly-Gly-Arg-Lys-Gln-Gly-Gln-His-Gln-Gln-Glu-Glu

Immunostimulating

In vitro and in vivo analysis in cell cultures and mice models

Gusa and Tani (2009)

Val-Ile-Lys

Anti-inflammatory activity

In vitro analysis in murine macrophage cell lines

(Dia et al (2014)

Tyr-Val-Pro-Gly-Pro

Anticancer activity

In vitro analysis on prostate cancer cells

Wu et al. (2018)

Ile-Pro

DPP-IV inhibition

In vitro analysis

Hatanaka et al. (2012)

Leu-Pro

Lys-Ala

DPP-IV inhibition

In vitro analysis

Gallego et al. (2014)

Ala-Ala-Ala-Thr-Pro

Arg-Trp

Antimicrobial activity

Increase in antimicrobial activity and hemolysis of red blood cells with increasing peptide chain length

Liu et al. (2007)

Arg-Trp-Arg-Trp

Arg-Trp-Arg-Trp-Arg-Trp

Arg-Trp-Arg-Trp-Arg-Trp-Arg-Trp

Arg-Trp-Arg-Trp-Arg-Trp-Arg-Trp-Arg-Trp

Val-Gln-Trp-Arg-Ile-Arg-Val-Ala-Val-Ile-Arg-Lys

Antimicrobial activity

60 mg/kg dose shown to be as effective as vancomycin in rats with Staphylococcus aureus

Wu et al. (2014)

Val-Leu-Leu-Val-Thr-Leu-Thr-Arg-Leu-His-Gln-Arg-Gly-Val-Ile-Tyr-Arg-Lys-Trp-Arg-His-Phe-Ser-Gly-Arg-Lys-Tyr-Arg

Antimicrobial activity

Antimicrobial studies with Escherichia coli DH5α, Bacillus subtilis AZ54, Staphylococcus aureus ATCC 6538 P and Pseudomonas aeruginosa strains

Pane et al. (2017)

Glu-Lys-Glu-Arg-Glu-Arg-Gln

ACE inhibition

Oral administration to spontaneously hypertensive rats (SHR) at a dose of 10 mg/kg body weight

Katayama et al. (2008)

Lys-Arg-Gln-Lys-Tyr-Asp-Ile

Lys-Arg-Val-Ile-Gln-Try

ACE inhibition

Oral administration to SHR at a dose of 10 mg/kg body weight

Muguruma et al. (2009)

Arg-Pro-Arg

ACE inhibition

Oral administration to SHR at a dose of 1 mg/kg body weight

Escudero et al. (2012)

Lys-Ala-Pro-Val-Ala

Pro-Thr-Pro-Val-Pro