Peptide–Peptide Co-Assembly: A Design Strategy for Functional Detection of C-peptide, A Biomarker of Diabetic Neuropathy
Diabetes-related neuropathy is a debilitating condition that may be averted if it can be detected early. One possible way this can be achieved at low cost is to utilise peptides to detect C-peptide, a biomarker of diabetic neuropathy. This depends on peptide-peptide co-assembly, which is currently i...
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/24/9671 |
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| author | Kiat Hwa Chan Jaehong Lim Joo Eun Jee Jia Hui Aw Su Seong Lee |
| author_facet | Kiat Hwa Chan Jaehong Lim Joo Eun Jee Jia Hui Aw Su Seong Lee |
| author_sort | Kiat Hwa Chan |
| collection | DOAJ |
| description | Diabetes-related neuropathy is a debilitating condition that may be averted if it can be detected early. One possible way this can be achieved at low cost is to utilise peptides to detect C-peptide, a biomarker of diabetic neuropathy. This depends on peptide-peptide co-assembly, which is currently in a nascent stage of intense study. Instead, we propose a bead-based triple-overlay combinatorial strategy that can preserve inter-residue information during the screening process for a suitable complementary peptide to co-assemble with C-peptide. The screening process commenced with a pentapeptide general library, which revealed histidine to be an essential residue. Further screening with seven tetrapeptide focused libraries led to a table of self-consistent peptide sequences that included tryptophan and lysine at high frequencies. Three complementary nonapeptides (9mer com-peptides), wpkkhfwgq (Trp-D), kwkkhfwgq (Lys-D), and KWKKHFWGQ (Lys-L) (as a negative control) were picked from this table for co-assembly studies with C-peptide. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) and circular dichroism (CD) spectroscopies were utilized to study inter-peptide interactions and changes in secondary structures respectively. ATR-FTIR studies showed that there is indeed inter-peptide interaction between C-peptide and the tryptophan residues of the 9mer com-peptides. CD studies of unaggregated and colloidal C-peptide with the 9mer com-peptides suggest that the extent of co-assembly of C-peptide with Trp-D is greatest, followed by Lys-D and Lys-L. These results are promising and indicate that the presented strategy is viable for designing and evaluating longer complementary peptides, as well as complementary peptides for co-assembly with other polypeptides of interest and importance. We discuss the possibility of designing complementary peptides to inhibit toxic amyloidosis with this approach. |
| first_indexed | 2024-03-10T13:57:58Z |
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| language | English |
| last_indexed | 2024-03-10T13:57:58Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-40f0d337a6ec41a6a2b5cbf9d5d455682023-11-21T01:27:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-012124967110.3390/ijms21249671Peptide–Peptide Co-Assembly: A Design Strategy for Functional Detection of C-peptide, A Biomarker of Diabetic NeuropathyKiat Hwa Chan0Jaehong Lim1Joo Eun Jee2Jia Hui Aw3Su Seong Lee4Division of Science, Yale-NUS College, 16 College Avenue West, Singapore 138527, SingaporeInstitute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, SingaporeInstitute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, SingaporeDivision of Science, Yale-NUS College, 16 College Avenue West, Singapore 138527, SingaporeInstitute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, SingaporeDiabetes-related neuropathy is a debilitating condition that may be averted if it can be detected early. One possible way this can be achieved at low cost is to utilise peptides to detect C-peptide, a biomarker of diabetic neuropathy. This depends on peptide-peptide co-assembly, which is currently in a nascent stage of intense study. Instead, we propose a bead-based triple-overlay combinatorial strategy that can preserve inter-residue information during the screening process for a suitable complementary peptide to co-assemble with C-peptide. The screening process commenced with a pentapeptide general library, which revealed histidine to be an essential residue. Further screening with seven tetrapeptide focused libraries led to a table of self-consistent peptide sequences that included tryptophan and lysine at high frequencies. Three complementary nonapeptides (9mer com-peptides), wpkkhfwgq (Trp-D), kwkkhfwgq (Lys-D), and KWKKHFWGQ (Lys-L) (as a negative control) were picked from this table for co-assembly studies with C-peptide. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) and circular dichroism (CD) spectroscopies were utilized to study inter-peptide interactions and changes in secondary structures respectively. ATR-FTIR studies showed that there is indeed inter-peptide interaction between C-peptide and the tryptophan residues of the 9mer com-peptides. CD studies of unaggregated and colloidal C-peptide with the 9mer com-peptides suggest that the extent of co-assembly of C-peptide with Trp-D is greatest, followed by Lys-D and Lys-L. These results are promising and indicate that the presented strategy is viable for designing and evaluating longer complementary peptides, as well as complementary peptides for co-assembly with other polypeptides of interest and importance. We discuss the possibility of designing complementary peptides to inhibit toxic amyloidosis with this approach.https://www.mdpi.com/1422-0067/21/24/9671peptide-peptideco-assemblydesigndetectionC-peptidebiomarker |
| spellingShingle | Kiat Hwa Chan Jaehong Lim Joo Eun Jee Jia Hui Aw Su Seong Lee Peptide–Peptide Co-Assembly: A Design Strategy for Functional Detection of C-peptide, A Biomarker of Diabetic Neuropathy International Journal of Molecular Sciences peptide-peptide co-assembly design detection C-peptide biomarker |
| title | Peptide–Peptide Co-Assembly: A Design Strategy for Functional Detection of C-peptide, A Biomarker of Diabetic Neuropathy |
| title_full | Peptide–Peptide Co-Assembly: A Design Strategy for Functional Detection of C-peptide, A Biomarker of Diabetic Neuropathy |
| title_fullStr | Peptide–Peptide Co-Assembly: A Design Strategy for Functional Detection of C-peptide, A Biomarker of Diabetic Neuropathy |
| title_full_unstemmed | Peptide–Peptide Co-Assembly: A Design Strategy for Functional Detection of C-peptide, A Biomarker of Diabetic Neuropathy |
| title_short | Peptide–Peptide Co-Assembly: A Design Strategy for Functional Detection of C-peptide, A Biomarker of Diabetic Neuropathy |
| title_sort | peptide peptide co assembly a design strategy for functional detection of c peptide a biomarker of diabetic neuropathy |
| topic | peptide-peptide co-assembly design detection C-peptide biomarker |
| url | https://www.mdpi.com/1422-0067/21/24/9671 |
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