Biological characterisation of somatropin-derived cryptic peptides

Show simple item record Tack, Liesa Bracke, Nathalie Verbeke, Frederick Wynendaele, Evelien Pauwels, Ewald Maes, Alex Van de Wiele, Christophe Sathekge, Mike Machaba De Spiegeleer, Bart 2018-09-19T05:29:28Z 2019-09
dc.description.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 (GHR). 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 and 120 min, were also identified. The interactions towards the 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. en_ZA
dc.description.department Nuclear Medicine en_ZA
dc.description.embargo 2019-08-21
dc.description.librarian hj2018 en_ZA
dc.description.sponsorship Grants from the Research Foundation FWO (Flanders) and NRF (South-Africa) (Grant No. G0G7617N) to Liesa Tack and from the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen) to Frederick Verbeke (Grant No. 131356). en_ZA
dc.description.uri en_ZA
dc.identifier.citation Tack, L., Bracke, N., Verbeke, F. et al. Biological Characterisation of Somatropin-Derived Cryptic Peptides. International Journal of Peptide Research and Therapeutics (2019) 25: 1019-1031. en_ZA
dc.identifier.issn 1573-3149 (print)
dc.identifier.issn 1573-3904 (online)
dc.identifier.other 10.1007/s10989-018-9749-y
dc.language.iso en en_ZA
dc.publisher Springer en_ZA
dc.rights © Springer Nature B.V. 2018. The original publication is available at : en_ZA
dc.subject Somatropin en_ZA
dc.subject Synthetic somatropin-derived peptide (SDP) en_ZA
dc.subject Growth hormone receptor (GHR) en_ZA
dc.subject Cryptic peptides en_ZA
dc.subject GHR bioassay en_ZA
dc.subject Native MS en_ZA
dc.subject Tissue distribution en_ZA
dc.subject Blood–brain barrier (BBB) en_ZA
dc.title Biological characterisation of somatropin-derived cryptic peptides en_ZA
dc.type Postprint Article en_ZA

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