Amino Acid Properties Reference
This reference provides systematic data for all 20 standard amino acids and non-standard amino acids commonly used in peptide synthesis. All values are for L-configurational amino acids at 25°C unless otherwise noted.
Standard Amino Acids
Section titled “Standard Amino Acids”Master Reference Table
Section titled “Master Reference Table”| Amino Acid | 3-Letter | 1-Letter | MW (Da) | α-COOH pKa | α-NH₃⁺ pKa | Side Chain pKa | pI | Hydrophobicity (Kyte-Doolittle) | Side Chain Classification |
|---|---|---|---|---|---|---|---|---|---|
| Glycine | Gly | G | 75.03 | 2.34 | 9.60 | — | 5.97 | −0.40 | Nonpolar, aliphatic |
| Alanine | Ala | A | 89.09 | 2.34 | 9.69 | — | 6.01 | 1.80 | Nonpolar, aliphatic |
| Valine | Val | V | 117.15 | 2.32 | 9.62 | — | 5.97 | 4.20 | Nonpolar, aliphatic |
| Leucine | Leu | L | 131.17 | 2.36 | 9.60 | — | 5.98 | 3.80 | Nonpolar, aliphatic |
| Isoleucine | Ile | I | 131.17 | 2.36 | 9.68 | — | 6.02 | 4.50 | Nonpolar, aliphatic |
| Proline | Pro | P | 115.13 | 1.99 | 10.96 | — | 6.48 | −1.60 | Nonpolar, aliphatic |
| Phenylalanine | Phe | F | 165.19 | 1.83 | 9.13 | — | 5.48 | 2.80 | Aromatic |
| Tyrosine | Tyr | Y | 181.19 | 2.20 | 9.11 | 10.07 | 5.66 | −1.30 | Aromatic, polar |
| Tryptophan | Trp | W | 204.23 | 2.38 | 9.39 | — | 5.89 | −0.90 | Aromatic |
| Serine | Ser | S | 105.09 | 2.21 | 9.15 | 13.00 | 5.68 | −0.80 | Polar, uncharged |
| Threonine | Thr | T | 119.12 | 2.63 | 10.43 | 13.00 | 6.53 | −0.70 | Polar, uncharged |
| Cysteine | Cys | C | 121.16 | 1.71 | 10.78 | 8.18 | 5.07 | 2.50 | Polar, uncharged |
| Methionine | Met | M | 149.21 | 2.28 | 9.21 | — | 5.74 | 1.90 | Nonpolar, sulfur |
| Asparagine | Asn | N | 132.12 | 2.02 | 8.80 | — | 5.41 | −3.50 | Polar, uncharged |
| Glutamine | Gln | Q | 146.15 | 2.17 | 9.13 | — | 5.65 | −3.50 | Polar, uncharged |
| Aspartic Acid | Asp | D | 133.10 | 1.88 | 9.60 | 3.65 | 2.77 | −3.50 | Negatively charged |
| Glutamic Acid | Glu | E | 147.13 | 2.19 | 9.67 | 4.25 | 3.22 | −3.50 | Negatively charged |
| Lysine | Lys | K | 146.19 | 2.18 | 8.95 | 10.53 | 9.74 | −3.90 | Positively charged |
| Arginine | Arg | R | 174.20 | 2.17 | 9.04 | 12.48 | 10.76 | −4.50 | Positively charged |
| Histidine | His | H | 155.16 | 1.82 | 9.17 | 6.00 | 7.59 | −3.20 | Positively charged |
Side Chain Details
Section titled “Side Chain Details”Nonpolar, Aliphatic
Section titled “Nonpolar, Aliphatic”| Amino Acid | Carbon Atoms | Branch Point | Key Feature |
|---|---|---|---|
| Glycine | 0 (H only) | None | Smallest; flexible backbone |
| Alanine | 1 (methyl) | None | Simplest chiral AA |
| Valine | 3 (isopropyl) | β-carbon | Branched at β-position |
| Leucine | 4 (isobutyl) | γ-carbon | Branched at γ-position |
| Isoleucine | 4 (sec-butyl) | β-carbon | 2 chiral centers |
| Proline | 3 (cyclic) | None | Cyclic; disrupts α-helix |
Aromatic
Section titled “Aromatic”| Amino Acid | Ring System | pKa (Side Chain) | UV Absorbance |
|---|---|---|---|
| Phenylalanine | Benzene | — | 257 nm (ε=200) |
| Tyrosine | Phenol | 10.07 | 274 nm (ε=1,400) |
| Tryptophan | Indole | — | 280 nm (ε=5,600) |
Polar, Uncharged
Section titled “Polar, Uncharged”| Amino Acid | Functional Group | H-Bond Capacity | Key Feature |
|---|---|---|---|
| Serine | Hydroxyl | Donor + acceptor | Phosphorylation site |
| Threonine | Hydroxyl | Donor + acceptor | Phosphorylation site |
| Cysteine | Thiol | Donor | Disulfide bonds; redox |
| Asparagine | Amide | Donor + acceptor | N-glycosylation site |
| Glutamine | Amide | Donor + acceptor | Ammonia transport |
Charged
Section titled “Charged”| Amino Acid | Charge at pH 7 | pKa | Role |
|---|---|---|---|
| Aspartic Acid | −1 | 3.65 | Acidic; salt bridges |
| Glutamic Acid | −1 | 4.25 | Acidic; catalytic |
| Lysine | +1 | 10.53 | Basic; ubiquitination |
| Arginine | +1 | 12.48 | Basic; guanidinium |
| Histidine | ~0 (pH 7) | 6.00 | Buffer; catalytic |
Codon Table
Section titled “Codon Table”| Amino Acid | 3-Letter | 1-Letter | Codons |
|---|---|---|---|
| Glycine | Gly | G | GGU, GGC, GGA, GGG |
| Alanine | Ala | A | GCU, GCC, GCA, GCG |
| Valine | Val | V | GUU, GUC, GUA, GUG |
| Leucine | Leu | L | UUA, UUG, CUU, CUC, CUA, CUG |
| Isoleucine | Ile | I | AUU, AUC, AUA |
| Proline | Pro | P | CCU, CCC, CCA, CCG |
| Phenylalanine | Phe | F | UUU, UUC |
| Tyrosine | Tyr | Y | UAU, UAC |
| Tryptophan | Trp | W | UGG |
| Serine | Ser | S | UCU, UCC, UCA, UCG, AGU, AGC |
| Threonine | Thr | T | ACU, ACC, ACA, ACG |
| Cysteine | Cys | C | UGU, UGC |
| Methionine | Met | M | AUG (start codon) |
| Asparagine | Asn | N | AAU, AAC |
| Glutamine | Gln | Q | CAA, CAG |
| Aspartic Acid | Asp | D | GAU, GAC |
| Glutamic Acid | Glu | E | GAA, GAG |
| Lysine | Lys | K | AAA, AAG |
| Arginine | Arg | R | CGU, CGC, CGA, CGG, AGA, AGG |
| Histidine | His | H | CAU, CAC |
Common Modifications
Section titled “Common Modifications”N-Terminal Modifications
Section titled “N-Terminal Modifications”| Modification | Effect | Use |
|---|---|---|
| Acetylation (Ac) | Blocks N-terminus; increases stability | Protease resistance |
| Biotinylation | Biotin tag | Affinity purification |
| Fmoc | Fluorenyl protecting group | SPPS synthesis |
| Boc | tert-Butyloxycarbonyl | SPPS synthesis |
| Dansyl | Fluorescent tag | Fluorescence studies |
C-Terminal Modifications
Section titled “C-Terminal Modifications”| Modification | Effect | Use |
|---|---|---|
| Amidation (NH₂) | Blocks C-terminus | Protease resistance |
| Thioester | Reactive handle | Native chemical ligation |
| tert-Butyl ester | Protecting group | SPPS synthesis |
| Wang resin | Solid support | SPPS synthesis |
Side Chain Modifications
Section titled “Side Chain Modifications”| Amino Acid | Modification | Effect |
|---|---|---|
| Cysteine | S-Acylation | Lipid conjugation |
| Cysteine | S-PEGylation | Half-life extension |
| Lysine | N-PEGylation | Half-life extension |
| Lysine | Acetylation | Charge neutralization |
| Arginine | Methylation | Altered binding |
| Aspartic acid | β-Asp formation | Isomerization (degradation) |
| Asparagine | Deamidation | Asp/isoAsp (degradation) |
| Methionine | Oxidation | Met sulfoxide (degradation) |
| Tryptophan | Oxidation | Trp oxindole (degradation) |
D-Amino Acid Substitutions
Section titled “D-Amino Acid Substitutions”| D-Amino Acid | Effect on Peptide |
|---|---|
| D-Ala | Protease resistance; conformational restriction |
| D-Phe | Protease resistance; altered receptor binding |
| D-Trp | Protease resistance; increased lipophilicity |
| D-Ser | Protease resistance; altered hydrogen bonding |
| D-Lys | Protease resistance; altered charge distribution |
Non-Standard Amino Acids in Peptide Synthesis
Section titled “Non-Standard Amino Acids in Peptide Synthesis”| Amino Acid | Abbreviation | MW (Da) | Feature |
|---|---|---|---|
| α-Aminoisobutyric acid | Aib | 101.13 | Helix stabilization; DPP-4 resistance |
| Norvaline | Nva | 117.15 | Leucine analog; protease resistance |
| Norleucine | Nle | 117.15 | Linear isomer; hydrophobic |
| Citrulline | Cit | 175.19 | Urea cycle intermediate |
| Homoserine | Hse | 119.12 | Serine analog; ligation handle |
| β-Alanine | β-Ala | 89.09 | β-amino acid; protease resistance |
| 4-Hydroxyproline | Hyp | 131.13 | Collagen modification; conformational |
| Desmosine | Des | 525.59 | Elastin crosslink |
| Hydroxylysine | Hyl | 162.19 | Collagen modification |
| Methyl-L-lysine | Me-Lys | 160.22 | Histone modification |
Properties Affecting Peptide Stability
Section titled “Properties Affecting Peptide Stability”| Property | Vulnerable Amino Acids | Degradation Pathway |
|---|---|---|
| Acid lability | Asp-Pro bonds | Acid hydrolysis |
| Base lability | — | β-elimination |
| Oxidation | Met, Cys, Trp, Tyr | ROS-mediated |
| Deamidation | Asn, Gln (Gly/Asn motifs) | pH/temperature-dependent |
| Isomerization | Asp, Asp-Gly motifs | D/L racemization |
| Proteolysis | All (site-dependent) | Enzymatic cleavage |
References
Section titled “References”- Nelson DL, Cox MM. Lehninger Principles of Biochemistry. 8th ed. W.H. Freeman; 2021.
- Kyte J, Doolittle RF. “A simple method for displaying the hydropathic character of a protein.” J Mol Biol 1982;157:105-132.
- Lewin B. Genes XII. Jones & Bartlett Learning; 2017.
- Wade LG. Organic Chemistry. 9th ed. Pearson; 2019.
- Chan WC, White PD. Fmoc Solid Phase Peptide Synthesis. Oxford University Press; 2000.