Current Protein & Peptide ScienceCurrent Protein & Peptide ScienceCurrent Protein & Peptide Science1389-20371875-5550Bentham Science64564010.2174/0113892037280719231214095428Life SciencesResearch ArticleThe Disulfide Bond-Mediated Cyclization of Oral PeptidesYaoChenguanginfo@benthamscience.netYeGuoguoinfo@benthamscience.netYangQininfo@benthamscience.netChenZhenwanginfo@benthamscience.netYangMinghuiinfo@benthamscience.netSino-German Biomedical Center, Hubei Provincial Key Laboratory of Industrial Microbiology, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Key Laboratory of Fermentation Engineering (Ministry of Education), National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of TechnologyNational Clinical Research Center for Infectious Disease, Second Hospital Affiliated to Southern University of Science and TechnologyCollege of Life Sciences, Wuhan UniversityCollege of Life Science and Technology, Huazhong University of Science and TechnologyKey Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology0106202425643844211012025Copyright ©; 2024, Bentham Science Publishers2024Bentham Science Publishershttps://journals.eco-vector.com/1389-2037/article/view/645640

‘Structure determines function’ is a consensus in the current biological community, but the structural characteristics corresponding to a certain function have always been a hot field of scientific exploration. A peptide is a bio-active molecule that is between the size of an antibody and a small molecule. Still, the gastrointestinal barrier and the physicochemical properties of peptides have always limited the oral administration of peptides. Therefore, we analyze the main ways oral peptide conversion strategies of peptide modification and permeation enhancers. Based on our analysis of the structure of natural oral peptides, which can be absorbed through the gastrointestinal tract, we believe that the design strategy of natural stapled peptides based on disulfide bonds is good for oral peptide design. This cannot only be used to identify anti-gastrointestinal digestive structural proteins in nature but also provide a solid structural foundation for the construction of new oral peptide drugs.

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