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Article

Synthetic Methods of Sugar Amino Acids and Their Application in the Development of Cyclic Peptide Therapeutics

College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China
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Processes 2025, 13(9), 2849; https://doi.org/10.3390/pr13092849
Submission received: 29 July 2025 / Revised: 21 August 2025 / Accepted: 28 August 2025 / Published: 5 September 2025
(This article belongs to the Special Issue Recent Advances in Bioprocess Engineering and Fermentation Technology)

Abstract

Sugar amino acids (SAAs) represent a privileged class of molecular chimeras that uniquely merge the structural rigidity of carbohydrates with the functional display of amino acids. These hybrid molecules have garnered significant attention as programmable conformational constraints, offering a powerful strategy to overcome the inherent limitations of peptide-based therapeutics, such as proteolytic instability and conformational ambiguity. The strategic incorporation of SAAs into peptide backbones, particularly within cyclic frameworks, allows for the rational design of peptidomimetics with pre-organized secondary structures, enhanced metabolic stability, and improved physicochemical properties. This review provides a comprehensive analysis of the synthetic methodologies developed to access the diverse structural landscape of SAAs, with a focus on modern, stereoselective strategies that yield versatile building blocks for peptide chemistry. A critical examination of the structural impact of SAA incorporation reveals their profound ability to induce and stabilize specific secondary structures, such as β- and γ-turns. Furthermore, a comparative analysis positions SAAs in the context of other widely used peptidomimetic scaffolds, highlighting their unique advantages in combining conformational control with tunable hydrophilicity. We surveyed the application of SAA-containing cyclic peptides as therapeutic agents, with a detailed case study on gramicidin S analogs that underscores the power of SAAs in elucidating complex structure–activity relationships. Finally, this review presents a forward-looking perspective on the challenges and future directions of the field, emphasizing the transformative potential of computational design, artificial intelligence, and advanced bioconjugation techniques to accelerate the development of next-generation SAA-based therapeutics.
Keywords: Glycoamino Acids; classification of Glycoamino Acids; synthesis of Glycoamino Acids; applications of Glycoamino Acids; cyclic peptides; combined application of Glycoamino Acids and cyclic peptides Glycoamino Acids; classification of Glycoamino Acids; synthesis of Glycoamino Acids; applications of Glycoamino Acids; cyclic peptides; combined application of Glycoamino Acids and cyclic peptides

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MDPI and ACS Style

Bao, C.; Wang, D. Synthetic Methods of Sugar Amino Acids and Their Application in the Development of Cyclic Peptide Therapeutics. Processes 2025, 13, 2849. https://doi.org/10.3390/pr13092849

AMA Style

Bao C, Wang D. Synthetic Methods of Sugar Amino Acids and Their Application in the Development of Cyclic Peptide Therapeutics. Processes. 2025; 13(9):2849. https://doi.org/10.3390/pr13092849

Chicago/Turabian Style

Bao, Chengcheng, and Dekai Wang. 2025. "Synthetic Methods of Sugar Amino Acids and Their Application in the Development of Cyclic Peptide Therapeutics" Processes 13, no. 9: 2849. https://doi.org/10.3390/pr13092849

APA Style

Bao, C., & Wang, D. (2025). Synthetic Methods of Sugar Amino Acids and Their Application in the Development of Cyclic Peptide Therapeutics. Processes, 13(9), 2849. https://doi.org/10.3390/pr13092849

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