Asset Details
Do you wish to reserve the book?
Differential stability of therapeutic peptides with different proteolytic cleavage sites in blood, plasma and serum
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Differential stability of therapeutic peptides with different proteolytic cleavage sites in blood, plasma and serum
Do you wish to request the book?
Differential stability of therapeutic peptides with different proteolytic cleavage sites in blood, plasma and serum
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Differential stability of therapeutic peptides with different proteolytic cleavage sites in blood, plasma and serum
2017
Overview
Proteolytic degradation of peptide-based drugs is often considered as major weakness limiting systemic therapeutic applications. Therefore, huge efforts are typically devoted to stabilize sequences against proteases present in serum or plasma, obtained as supernatants after complete blood coagulation or centrifugation of blood supplemented with anticoagulants, respectively. Plasma and serum are reproducibly obtained from animals and humans allowing consistent for clinical analyses and research applications. However, the spectrum of active or activated proteases appears to vary depending on the activation of proteases and cofactors during coagulation (serum) or inhibition of such enzymes by anticoagulants (plasma), such as EDTA (metallo- and Ca2+-dependent proteases) and heparin (e.g. thrombin, factor Xa). Here, we studied the presumed effects on peptide degradation by taking blood via cardiac puncture of CD-1 mice using a syringe containing a peptide solution. Due to absence of coagulation activators (e.g. glass surfaces and damaged cells), visible blood clotting was prevented allowing to study peptide degradation for one hour. The remaining peptide was quantified and the degradation products were identified using mass spectrometry. When the degradation rates (half-life times) were compared to serum derived freshly from the same animal and commercial serum and plasma samples, peptides of three different families showed indeed considerably different stabilities. Generally, peptides were faster degraded in serum than in plasma, but surprisingly all peptides were more stable in fresh blood and the order of degradation rates among the peptides varied among the six different incubation experiments. This indicates, that proteolytic degradation of peptide-based therapeutics may often be misleading stimulating efforts to stabilize peptides at degradation sites relevant only in vitro, i.e., for serum or plasma stability assays, but of lower importance in vivo.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Analysis
/ Animals
/ Antimicrobial Cationic Peptides - blood
/ Antimicrobial Cationic Peptides - chemistry
/ Antimicrobial Cationic Peptides - metabolism
/ Assaying
/ Blood
/ Blood Specimen Collection - methods
/ Cadmium
/ Calcium
/ Cleavage
/ Clotting
/ Drugs
/ Enzymes
/ Ethylenediaminetetraacetic acids
/ Female
/ Glass
/ Heart
/ Heparin
/ Medicine and Health Sciences
/ Mice
/ Peptides
/ Thrombin
