Predictive selection and evaluation of appropriate functional peptides for intestinal delivery with a porous silica gel

https://doi.org/10.1016/j.jbiosc.2019.01.001Get rights and content

Bioactive peptides have a positive impact on body functions and conditions and may influence health. However, peptides are degraded by digestive enzymes, such as pepsin in the stomach when ingested orally. In order to solve this problem, we previously focused on porous silica gel and found that by using calcined silica gel, hydrophobic and negatively charged peptides could be efficiently delivered into the intestine, because peptides adsorbed on the cavity of the silica gel could be protected from enzymatic degradation. Therefore, in this study, we attempted to develop peptides whose physicochemical properties were suitable for intestinal delivery without lowering their activity. We also proposed guidelines of predictive selection of such peptides. For that purpose, we selected hypercholesterolemic peptides as a model and re-designed the peptides based on the previously reported color map, in which intestinal delivery degree was predictively depicted as contour lines. As a result, we succeeded in getting five different re-designed peptides from 1265 substituted peptide derivatives. These peptides showed a dual function of being suitable for intestinal delivery with silica gel and for disruption of bile acid micelles. The release amount of IYEYMY was 2.09 times the parent peptide, which was the highest.

Section snippets

Materials

Porous silica gel, SMB-100-5 was supplied by Fuji Silysia Chemical Ltd., Aichi, Japan. Heat-treated silica gel was created from SMB-100-5 by calcining at 600 °C for 2 h under an air atmosphere (FG31, Yamato Scientific Co., Ltd., Tokyo, Japan).

Peptide synthesis for the evaluation of adsorption properties of silica

Peptide arrays were synthesized using a cellulose membrane and a spot synthesizer (ASP222, Intervis, Cologne, Germany) as previously described (18). After punching, each of the resulting peptide-containing disks (peptide spots) was placed in a single well

Drawing a hexa-peptide color map and peptide screening

In our previous report, we prepared color maps in which degree of intestinal delivery were predicted and depicted as contour lines. In these maps, score values of 32 tri-, penta-, and hepta- peptides were depicted. In the present study, a new color map was drawn with hexa-peptide library in the same way. We selected 32 kinds of peptides with varying hydrophobicity and pI (Fig. 1A), conducted adsorption experiments, and calculated score values (Table S1). Based on these results, we drew a

Acknowledgments

This work was partially supported by Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant Numbers: JP16H04575), Japan and Aichi Science and Technology Foundation (17J6401b), Japan. We would like to thank Editage for English language editing.

References (26)

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