Peptide–Peptide Co-Assembly: A Design Strategy for Functional Detection of C-peptide, A Biomarker of Diabetic Neuropathy

International Journal of Molecular Sciences

卷:21

KiatHwa Chan¹  JiaHui Aw¹  Jaehong Lim²  SuSeong Lee²  JooEun Jee² 

[1] Division of Science, Yale-NUS College, 16 College Avenue West, Singapore 138527, Singapore;

[2] Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore;

关键词: peptide-peptide;    co-assembly;    design;    detection;    C-peptide;    biomarker;   

DOI  :  10.3390/ijms21249671

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown