Heterotrimeric collagen peptides containing functional epitopes. Synthesis of single-stranded collagen type I peptides related to the collagenase cleavage site.
Journal of peptide science : an official publication of the European Peptide Society
confidence
Key findings
Methods paper: optimized Fmoc/tBu synthesis of collagen-type peptides using Fmoc-Pro-Hyp-Gly-OH synthon; no clinical/biological endpoints.
View source on PubMed (PMID 10100126) ↗
- Sample size
- N/A
- Population
- N/A - synthetic chemistry methods study
- Dosing
- N/A
- Duration
- N/A
- Route
- N/A
- Blinding
- not_reported
- Controls
- not_reported
- Drug class
- peptide
Full abstract
Synthetic collagen peptides containing larger numbers of Gly-Pro-Hyp repeats are difficult to purify by standard chromatographic procedures. Therefore, efficient strategies are required for the synthesis of higher molecular weight collagen-type peptides. Applying the Fmoc/tBu chemistry, a comparative analysis of the standard stepwise chain elongation procedure on solid support with the procedure based on the use of the synthons Fmoc-Gly-Pro-Hyp(tBu)-OH and Fmoc-Pro-Hyp-Gly-OH was performed. The crude products resulting from the stepwise elongation procedure and from the use of Fmoc-Gly-Pro-Hyp(tBu)-OH clearly revealed large amounts of microheterogeneities that result from incomplete imino acid acylation as well as from diketopiperazine formation with cleavage of Gly-Pro units from the growing peptide chain. Conversely, by the use of the Fmoc-Pro-Hyp-Gly-OH synthon, the quality of the crude products was significantly improved; moreover, protection of the Hyp side chain hydroxyl function is not required using the Fmoc/tBu strategy. With this optimized synthetic procedure, relatively large collagen-type peptides were obtained in satisfactory yields as highly homogeneous compounds.