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Biological characterisation of somatropin-derived cryptic peptides

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Abstract
Little is known about possible cryptic peptides of the recombinant growth hormone (somatropin). In this study, six synthetic somatropin-derived peptides (SDPs) were selected based on their sequences which correspond to the binding interface of the growth hormone receptor. Their novelty was confirmed by in silico and in vitro proteolytic digestion of somatropin. Chemical characterisation of the SDPs, i.e. identification via LC-MS and purity quantification via HPLC-UV and U(H)PLC-MRM, was first performed. All the SDPs were stable in brain tissue homogenate, liver tissue homogenate and serum (t1/2 > 15 min). The metabolites in brain and serum, formed between 15 min and 120 min, were also identified. The interactions towards the growth hormone receptor (GHR) and the human growth hormone binding protein (hGHBp) were also evaluated using GHR bioassay and native MS. No interaction was detected under the applied conditions. A last part of the study investigated the pharmacokinetics and tissue distribution of two peptides (i.e. SDP167-175 and SDP101-121), selected based on their position within somatropin. A high blood-brain barrier (BBB) influx was observed for SDP101-121, while SDP167-175 showed a negligible BBB influx. Based on the obtained results, the GHR binding of the selected SDPs is very low, requiring structural adaptations for further GHR-binding exploration.
Keywords
somatropin, cryptic peptides, GHR bioassay, native MS, tissue distribution, BBB distribution

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Citation

Please use this url to cite or link to this publication:

Chicago
Tack, Liesa, Nathalie Bracke, Frederick Verbeke, Evelien Wynendaele, Ewald Pauwels, Alex Maes, Christophe Van de Wiele, Mike Sathekge, and Bart De Spiegeleer. 2019. “Biological Characterisation of Somatropin-derived Cryptic Peptides.” International Journal of Peptide Research and Therapeutics.
APA
Tack, Liesa, Bracke, N., Verbeke, F., Wynendaele, E., Pauwels, E., Maes, A., Van de Wiele, C., et al. (2019). Biological characterisation of somatropin-derived cryptic peptides. INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS.
Vancouver
1.
Tack L, Bracke N, Verbeke F, Wynendaele E, Pauwels E, Maes A, et al. Biological characterisation of somatropin-derived cryptic peptides. INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS. 2019;
MLA
Tack, Liesa, Nathalie Bracke, Frederick Verbeke, et al. “Biological Characterisation of Somatropin-derived Cryptic Peptides.” INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS (2019): n. pag. Print.
@article{8575288,
  abstract     = {Little is known about possible cryptic peptides of the recombinant growth hormone (somatropin). In this study, six synthetic somatropin-derived peptides (SDPs) were selected based on their sequences which correspond to the binding interface of the growth hormone receptor. Their novelty was confirmed by in silico and in vitro proteolytic digestion of somatropin. Chemical characterisation of the SDPs, i.e. identification via LC-MS and purity quantification via HPLC-UV and U(H)PLC-MRM, was first performed. All the SDPs were stable in brain tissue homogenate, liver tissue homogenate and serum (t1/2 {\textrangle} 15 min). The metabolites in brain and serum, formed between 15 min and 120 min, were also identified. The interactions towards the growth hormone receptor (GHR) and the human growth hormone binding protein (hGHBp) were also evaluated using GHR bioassay and native MS. No interaction was detected under the applied conditions. A last part of the study investigated the pharmacokinetics and tissue distribution of two peptides (i.e. SDP167-175 and SDP101-121), selected based on their position within somatropin. A high blood-brain barrier (BBB) influx was observed for SDP101-121, while SDP167-175 showed a negligible BBB influx. Based on the obtained results, the GHR binding of the selected SDPs is very low, requiring structural adaptations for further GHR-binding exploration.},
  author       = {Tack, Liesa and Bracke, Nathalie and Verbeke, Frederick and Wynendaele, Evelien and Pauwels, Ewald and Maes, Alex and Van de Wiele, Christophe and Sathekge, Mike and De Spiegeleer, Bart},
  issn         = {1573-3149},
  journal      = {INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS},
  language     = {eng},
  title        = {Biological characterisation of somatropin-derived cryptic peptides},
  url          = {http://dx.doi.org/10.1007/s10989-018-9749-y},
  year         = {2019},
}

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