What is a β-Amino acid?

You might be familiar with α amino acids, which are building blocks of proteins. But why is it called an α amino acid? It’s based on the position of amino group attached to it. Amino group is attached to α & and β positions respectively in α & and β amino acids. See the figure below to get the nomenclature clear

https://upload.wikimedia.org/wikipedia/commons/thumb/9/92/Beta_alanine_comparison.svg/368px-Beta_alanine_comparison.svg.png

You can also see https://www.youtube.com/watch?v=nTKk2zdyiS4

Why do you bother about a β amino acid, if it’s not common in nature?

β-Amino acids are also found in peptides and specific heterocycles, although they are less significant than their α-analogues, and their free forms and derivatives have interesting biological and pharmacological effects. The only common β-Amino acid that occurs naturally is β-alanine (3-aminopropanoic acid). Carnosine & Anserine (both function as excellent buffer to maintain physiological pH) are two dipeptides containing β-alanine which are present in our brain and muscle tissues. Another two important biologically important molecules containing β-alanine residue are Pantothenic acid (also known as vitamin B₅ & Coenzyme A. There are numerous other occurrences of β residues in nature as part of a bigger molecules¹ which could be broadly classified as (1) Nonribosomal peptides and their hybrids with polyketides, (2) Macrolactam polyketides (3) Polyketide–β-amino acid hybrids (3) Terpenoid–β-amino acid hybrids & (4) Sugar–β-amino acid hybrids. Among this is a recent finding of the presence of another β-amino acid called β‐aminobutyric acid (BABA) in plants².

β-amino acid residue seen in nature are generally derived from proteinogenic α-amino acids. Even though nature is limited in this way in making use of β-amino acid residue, chemists are not. Chemists realized the real potential of β-amino acid residues especially after the seminal work of Dieter Seebach³ and Samuel Gellman⁴ in 1996. From that time onwards chemists had synthesized different types of β-amino acid based on the substituents and pattern of substitution on Cα & Cβ carbons of β residue. Foldamers based on β-amino acid residues had potential material science and biological applications. β-amino acid based foldamers could fold into different types of helices like the ones formed by α amino acid residues and more unique types of helices. They have excellent potential pharmacological applications due to the possibility in mimicking the secondary structures of proteinogenic α amino acids and also due to its resistance towards mammalian proteases⁵.

Reference

1.  Kudo, F.; Miyanaga, A.; Eguchi, T. Biosynthesis of Natural Products Containing β-Amino Acids. Natural Product Reports. 2014. https://doi.org/10.1039/c4np00007b.
2. Thevenet, D.; Pastor, V.; Baccelli, I.; Balmer, A.; Vallat, A.; Neier, R.; Glauser, G.; Mauch-Mani, B. The Priming Molecule β-Aminobutyric Acid Is Naturally Present in Plants and Is Induced by Stress. New Phytol. 2017. https://doi.org/10.1111/nph.14298.
3. Seebach, D.; Overhand, M.; Kühnle, F. N. M.; Martinoni, B.; Oberer, L.; Hommel, U.; Widmer, H. 80. β-Peptides: Synthesis by Arndt-Eistert Homologation with Concomitant Peptide Coupling. Structure Determination by NMR and CD Spectroscopy and by X-Ray Crystallography. Helical Secondary Structure of a β-Hexapeptide in Solution and Its Stability towards Pepsin. Helv. Chim. Acta 1996, 79 (4), 913–941. https://doi.org/10.1002/hlca.19960790402.
4. Appella, D. H.; Christianson, L. A.; Karle, I. L.; Powell, D. R.; Gellman, S. H. β-Peptide Foldamers: Robust Helix Formation in a New Family of β-Amino Acid Oligomers. J. Am. Chem. Soc. 1996. https://doi.org/10.1021/ja963290l.
5. Seebach, D.; Beck, A. K.; Bierbaum, D. J. The World of β- And γ-Peptides Comprised of Homologated Proteinogenic Amino Acids and Other Components. Chemistry and Biodiversity. 2004. https://doi.org/10.1002/cbdv.200490087.