Chain Extension: Discover Homo Amino Acids

Homo amino acids are non-canonical analogs of amino acids, in which their side chains are elongated by one or more methylene (-CH₂-) groups. Regarding their nomenclature, the letter "h" is added to the three-letter-code abbreviation of the amino acid, and, if more than one methylene group is inserted, a number indicates how many of them are added. E.g., in H2Lys, the side chain is made of six methylene groups, instead of four in “native” lysine.

Such homo amino acids may be used to substitute canonical amino acids, e.g., to modulate proteolytic and conformational stability of a synthesized peptide, to improve oral bioavailability, to increase its hydrophobicity, or binding selectivity.

Homolysines for example are efficient substrates for histone acetyltransferases, homoarginines may serve as substrates for the enzyme NO-synthase. Homoserines allow for late-stage synthetic functionalization of peptides, e.g., for combinatorial syntheses of methionine-like thioethers, selenoethers, thioglycosides, pyridinium salts, and fluorescent labels. Peptides with incorporated homo amino acids also are useful for the study of amino acid modifying enzymes like kinases.

Herein, we present six novel homo amino acid building blocks suitable for Fmoc peptide synthesis: H2Lys and H3Lys, H2Ser and H4Ser, H4Glu and H2Arg.

Structures of the Fmoc and Boc protected homolysine building blocks Fmoc-L-H2Lys(Boc)-OH (FAA9430) and Fmoc-L-H3Lys(Boc)-OH (FAA9435).

Chemical structures of the Fmoc and tBu-protected homoserine building blocks Fmoc-L-H2Ser(tBu)-OH (FAA9470) and Fmoc-L-H4Ser(tBu)-OH (FAA9475).

Chemical structures of the Fmoc and tBu/Pbf-protected glutamate and arginine building blocks Fmoc-L-H4Glu(OtBu)-OH (FAA9510) and Fmoc-L-H2Arg(Pbf)-OH (FAA9515).

→ Find more homo amino acid building blocks in our catalogue!

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References:

Effect of lysine side chain length on histone lysine acetyltransferase catalysis; G. Proietti, Y. Wang, G. Rainone, J. Mecinovic; Sci. Rep. 2020; 10: 13046. https://doi.org/10.1038/s41598-020-69510-0

Homoarginine, arginine, and relatives: analysis, metabolism, transport, physiology, and pathology; D. Tsikas, G. Wu; Amino Acids 2015; 47: 1697-1702. https://doi.org/10.1007/s00726-015-2055-5

Special Issue: Homoarginine, arginine and relatives; D. Tsikas, G. Wu; Amino Acids 2015; 47. https://link.springer.com/collections/eiffhicdjb

Shorter arginine homologues to stabilize peptides towards tryptic digestion; P. Henklein, T. Bruckdorfer; Chem. Today 2018; 26(6): 12-15.

Short arginine analogs: peptide synthesis and prediction of biological effects; T. A. Dzimbova, P. Henklein, T. Bruckdorfer, R. M. Maier, M. W. Weishaupt, T. I. Pajpanova; Chem. Today 2019; 37(2): 28-33.

Late-stage functionalisation of peptides on the solid phase by an iodination-substitution approach; M. Werner, J. Pampel, T. L. Pham, F. Thomas; Chem. Eur. J. 2022; 28: e202201339. https://doi.org/10.1002/chem.202201339

Synthesis of homoserine phospho-, H-phosphono- and methylphosphonopeptides; A. Tholey, R. Pipkorn, M. Zeppezauer, J. Reed; Lett. Pept. Sci. 1998; 5: 263-268. https://doi.org/10.1023/A:1008841621754