Leucine (Leu, L)
Leucine is a hydrophobic amino acid with a branched aliphatic side chain. It is one of the strongest helix formers and dominates the non-polar faces of amphipathic and coiled-coil peptides.
Structure and properties
Leucine has a four-carbon side chain branched at the gamma carbon, ending in an isopropyl group. Because the branch is further from the backbone than in isoleucine or valine, leucine does not crowd the backbone and strongly favours alpha-helical structure. The side chain is entirely aliphatic and strongly hydrophobic. Leucine is among the most abundant amino acids in proteins, where it packs in hydrophobic cores and at helix-helix interfaces. Its regular spacing every seventh residue defines the leucine zipper, a coiled-coil motif in which helices interlock along a stripe of leucines.
Role in peptides
Leucine-rich amphipathic helices are a common design for membrane-active and antimicrobial peptides. LL-37 begins with two leucines and carries more on its hydrophobic face. Leucine is part of the C-terminal Gly-Leu-Arg-Phe-NH2 region of Kisspeptin-10 and appears in the helical region of GLP-1 analogues. Norleucine, a straight-chain isomer, is often used as an oxidation-resistant replacement for methionine, as in Melanotan II and PT-141. BPC-157 contains leucine near its C-terminus. Leucine is also a common replacement when designers need a helix-stabilising hydrophobic residue.
Stability and analysis
Leucine has few specific concerns. Its side chain is chemically inert and it couples well in synthesis. As with isoleucine, the main analytical point is that leucine and isoleucine are isobaric and cannot be distinguished by intact mass or by standard fragmentation, so identity confirmation relies on synthesis records, amino acid analysis or specialised methods. Leucine-rich peptides can be poorly soluble in water and may self-associate, broadening or splitting HPLC peaks.
In PeptideWiki compounds
Compounds whose sequence contains leucine, with the number of occurrences.
- Abaloparatide (8)
- IGF-1 LR3 (8)
- CJC-1295 (5)
- Calcitonin (salmon) (5)
- Humanin (5)
- Teriparatide (5)
- Tesamorelin (5)
- LL-37 (4)
- Sermorelin (4)
- Exenatide (3)
- Pramlintide (3)
- VIP (vasoactive intestinal peptide) (3)
- ARA-290 (cibinetide) (2)
- Thymosin β4 (2)
- AOD-9604 (1)
- BPC-157 (1)
- Gonadorelin (1)
- Kisspeptin-10 (1)
- Larazotide (1)
- MOTS-c (1)
- Oxytocin (1)
- TB-500 (1)
- Thymosin α1 (1)
- Triptorelin (1)
Frequently asked questions
What is a leucine zipper?
A leucine zipper is a coiled-coil motif in which leucines recur at every seventh position of an alpha helix. Because a helix turns about every three and a half residues, these leucines line up along one face. Two such helices pair by interlocking their leucine faces like a zipper. The motif is common in transcription factors and is widely used in peptide design to drive controlled dimerisation.
Why is norleucine used in place of methionine?
Norleucine has a straight four-carbon side chain of similar size and shape to methionine's, but with a methylene group in place of sulfur. It therefore mimics methionine's packing without the oxidation liability of the thioether. Melanocortin analogues such as Melanotan II and PT-141 use norleucine at the position occupied by methionine in alpha-MSH, which removes a major degradation route.
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