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Vol. 24, Art. 75 (pp. 1097-1110)    |    2023       

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Methods for chemical modification of peptides to increase their oral bioavailability (Literature review)

Orlova A.B., Nikiforov A.S., Ivanov I.M., Ruipo V.S.

FSBI «State Research Testing Institute of Military Medicine» of the Ministry of Defense of the Russian Federation

Brief summary

The review considers the problem of oral administration of peptides, as well as approaches to increasing their bioavailability through chemical modification aimed at optimizing the physicochemical and pharmacological properties. The following strategies are considered as applied strategies: changing the initial structure of the peptide, introducing lipophilic and non-proteinogenic amino acids, including a number of D- and N-methylated amino acid residues. The possibilities of cyclization of peptide structures using various approaches have also been demonstrated, such as cyclization of the main chain or «head to tail» (N-terminus to C-terminus), side chain to side chain, side chain to the end, cyclization to form a disulfide or thioether bonds. As examples of orally available peptides were considered: a peptide developed for the treatment of autoimmune diseases; a modified derivative of the peptide antibiotic griselymycin; a synthetic analogue of vasopressin - desmopressin, as well as an immunosuppressant cyclosporine and a modified clam-derived cyclic peptide.


Key words

peptides, oral bioavailability, chemical modification

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