# A Convenient Synthesis of Short α-/β-Mixed Peptides as Potential α-Amylase Inhibitors

## TL;DR

This paper describes a new method to synthesize short peptides that may help control blood sugar by inhibiting the α-amylase enzyme.

## Contribution

A novel synthesis method for α-/β-mixed peptides with potential α-amylase inhibition is introduced.

## Key findings

- Three novel α-/β-mixed peptides were successfully synthesized and characterized.
- Peptide 16 showed the highest α-amylase inhibition at 45.22%.
- The synthesis method avoids racemization and retains configuration.

## Abstract

Over the last decades, the increased incidence of metabolic disorders, such as type two diabetes and obesity, has motivated researchers to investigate new enzyme inhibitors. Inhibition of the α-amylase enzyme is one therapeutic approach in lowering glucose levels in the blood to manage diabetes mellitus. The objective of this study was to synthesize short α-/β-mixed peptides in the solution phase. The Boc-protected α-L-leucine was converted to β-analogue by using Arndt–Eistert synthesis with the advantage of no racemization and retention of configuration. Three novel short peptides were successfully synthesized: N(Boc)-Gly-β-Leu–OCH3(14), N(Boc)-O(Bz)α-Ser-β-Leu–OCH3(16), and N(Boc)-O(Bz)-α-Tyr-α-Gly-β-Leu–OCH3(17), characterized by FTIR and 1H NMR analysis. The synthesized peptide 16 showed highest inhibitory activity (45.22%) followed by peptide 14 (18.51%) and peptide 17 (17.05%), respectively. Intriguingly, peptide 16 showed higher inhibition on α-amylase compared with other α-/β-mixed peptides.