2022
DOI: 10.1038/s42003-022-03015-6
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Single-chain tandem macrocyclic peptides as a scaffold for growth factor and cytokine mimetics

Abstract: Mimetics of growth factors and cytokines are promising tools for culturing large numbers of cells and manufacturing regenerative medicine products. In this study, we report single-chain tandem macrocyclic peptides (STaMPtides) as mimetics in a new multivalent peptide format. STaMPtides, which contain two or more macrocyclic peptides with a disulfide-closed backbone and peptide linkers, are successfully secreted into the supernatant by Corynebacterium glutamicum-based secretion technology. Without post-secretio… Show more

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Cited by 8 publications
(12 citation statements)
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“…In fact, Vi‐STaMPtide‐PA16, which showed enhanced affinity and more than 1000‐fold stronger inhibitory activity against VEGFR2 than its parent monomeric macrocyclics, was discovered using a straightforward design of STaMPtides and rapid activity evaluation. We conclude that dimerization as a STaMPtide format is a promising strategy for obtaining potent PPI inhibitor and growth factor mimetics, which we previously demonstrated, [31] because it is easier to design, manufacture, and optimize than other multivalent biological conjugates, such as antibodies, tandem fragment antibodies, and antibody mimetics. Further evaluations are underway to confirm their suitability for pharmaceutical use, including plasma stability, pharmacokinetics, and in vivo efficacy.…”
Section: Discussionmentioning
confidence: 77%
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“…In fact, Vi‐STaMPtide‐PA16, which showed enhanced affinity and more than 1000‐fold stronger inhibitory activity against VEGFR2 than its parent monomeric macrocyclics, was discovered using a straightforward design of STaMPtides and rapid activity evaluation. We conclude that dimerization as a STaMPtide format is a promising strategy for obtaining potent PPI inhibitor and growth factor mimetics, which we previously demonstrated, [31] because it is easier to design, manufacture, and optimize than other multivalent biological conjugates, such as antibodies, tandem fragment antibodies, and antibody mimetics. Further evaluations are underway to confirm their suitability for pharmaceutical use, including plasma stability, pharmacokinetics, and in vivo efficacy.…”
Section: Discussionmentioning
confidence: 77%
“…This design enables STaMPtides to comprise two disulfide‐linked macrocyclic peptides in a single‐chain. Because optimizing the linker length and sequence is highly important to obtain the desirable potency of bivalent peptides, [31] we constructed several linker variants of Vi‐STaMPtides as candidates. For the peptide linker sequence, conventional glycine‐serine (GS)‐repeat and proline‐alanine (PA)‐repeat, which were previously applied to STaMPtides, [31] were chosen.…”
Section: Resultsmentioning
confidence: 99%
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“…To overcome the limitation, investigators have screened surrogate ligands that activate cytokine receptors. Antibodies [ 7 ], peptides [ 8 ], nucleic acids [ 9 ], and even small molecules [ 10 ] have been reported to function as agonists at cytokine receptors. However, since the conformation is important for activation of cytokine receptors, these agonists do not always retain the same levels of receptor activation capability as natural cytokines [ 11 ].…”
Section: Introductionmentioning
confidence: 99%