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Cyclic thrombospondin-1 mimetics: grafting of a thrombospondin sequence into circular disulfide-rich frameworks to inhibit endothelial cell migration.

Chan LY, Craik DJ, Daly NL - Biosci. Rep. (2015)

Bottom Line: Importantly, all of the designed cyclic TSP-1 mimetics were far more stable than the linear heptapeptide in human serum.The present study has demonstrated a novel approach to stabilize the active region of TSP-1.The anti-angiogenic activity of the native TSP-1 active fragment was maintained in the new TSP-1 mimetics and the results provide a new chemical approach for the design of TSP-1 mimetics.

View Article: PubMed Central - PubMed

Affiliation: The University of Queensland, Institute for Molecular Bioscience, Brisbane 4072, Queensland, Australia.

No MeSH data available.


Related in: MedlinePlus

NMR analysis of cyclic TSP-1 mimetics(A) Comparison of SFTI-1 and SFTI-TSP-1 αH chemical shifts. (B) Comparison of MCoTI-II and MCo-TSP-1 αH chemical shifts. All 1H NMR spectra were recorded at 298 K. The active TSP-1 fragment is highlighted in bold and the region for comparing native and inserted sequence in different cyclic frameworks is in a grey box. Disulfide bond connectivity is indicated with bold lines and each cysteine is labelled with Roman numerals.
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Figure 2: NMR analysis of cyclic TSP-1 mimetics(A) Comparison of SFTI-1 and SFTI-TSP-1 αH chemical shifts. (B) Comparison of MCoTI-II and MCo-TSP-1 αH chemical shifts. All 1H NMR spectra were recorded at 298 K. The active TSP-1 fragment is highlighted in bold and the region for comparing native and inserted sequence in different cyclic frameworks is in a grey box. Disulfide bond connectivity is indicated with bold lines and each cysteine is labelled with Roman numerals.

Mentions: It was important to analyse the structure of the newly designed cyclic TSP-1 analogues to determine whether these peptides adopt similar conformations to their native frameworks. In general, the αH NMR chemical shifts of MCo-TSP-1 and SFTI-TSP-1 were found to be similar to MCoTI-II and SFTI-1, respectively, which indicates that the native fold was maintained in the grafted peptides (Figure 2). There were some differences in αH NMR chemical shifts at the grafted regions, but this was expected due to the differences in amino acid residues in these regions.


Cyclic thrombospondin-1 mimetics: grafting of a thrombospondin sequence into circular disulfide-rich frameworks to inhibit endothelial cell migration.

Chan LY, Craik DJ, Daly NL - Biosci. Rep. (2015)

NMR analysis of cyclic TSP-1 mimetics(A) Comparison of SFTI-1 and SFTI-TSP-1 αH chemical shifts. (B) Comparison of MCoTI-II and MCo-TSP-1 αH chemical shifts. All 1H NMR spectra were recorded at 298 K. The active TSP-1 fragment is highlighted in bold and the region for comparing native and inserted sequence in different cyclic frameworks is in a grey box. Disulfide bond connectivity is indicated with bold lines and each cysteine is labelled with Roman numerals.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4660582&req=5

Figure 2: NMR analysis of cyclic TSP-1 mimetics(A) Comparison of SFTI-1 and SFTI-TSP-1 αH chemical shifts. (B) Comparison of MCoTI-II and MCo-TSP-1 αH chemical shifts. All 1H NMR spectra were recorded at 298 K. The active TSP-1 fragment is highlighted in bold and the region for comparing native and inserted sequence in different cyclic frameworks is in a grey box. Disulfide bond connectivity is indicated with bold lines and each cysteine is labelled with Roman numerals.
Mentions: It was important to analyse the structure of the newly designed cyclic TSP-1 analogues to determine whether these peptides adopt similar conformations to their native frameworks. In general, the αH NMR chemical shifts of MCo-TSP-1 and SFTI-TSP-1 were found to be similar to MCoTI-II and SFTI-1, respectively, which indicates that the native fold was maintained in the grafted peptides (Figure 2). There were some differences in αH NMR chemical shifts at the grafted regions, but this was expected due to the differences in amino acid residues in these regions.

Bottom Line: Importantly, all of the designed cyclic TSP-1 mimetics were far more stable than the linear heptapeptide in human serum.The present study has demonstrated a novel approach to stabilize the active region of TSP-1.The anti-angiogenic activity of the native TSP-1 active fragment was maintained in the new TSP-1 mimetics and the results provide a new chemical approach for the design of TSP-1 mimetics.

View Article: PubMed Central - PubMed

Affiliation: The University of Queensland, Institute for Molecular Bioscience, Brisbane 4072, Queensland, Australia.

No MeSH data available.


Related in: MedlinePlus