Stereochemistry of Amino Acid Spacers Determines the Pharmacokinetics of (111)In-DOTA-Minigastrin Analogues for Targeting the CCK2/Gastrin Receptor.
Data(s) |
17/06/2015
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Resumo |
The metabolic instability and high kidney retention of minigastrin (MG) analogues hamper their suitability for use in peptide-receptor radionuclide therapy of CCK2/gastrin receptor-expressing tumors. High kidney retention has been related to N-terminal glutamic acids and can be substantially reduced by coinjection of polyglutamic acids or gelofusine. The aim of the present study was to investigate the influence of the stereochemistry of the N-terminal amino acid spacer on the enzymatic stability and pharmacokinetics of (111)In-DOTA-(d-Glu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 ((111)In-PP11-D) and (111)In-DOTA-(l-Glu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 ((111)In-PP11-L). Using circular dichroism measurements, we demonstrate the important role of secondary structure on the pharmacokinetics of the two MG analogues. The higher in vitro serum stability together with the improved tumor-to-kidney ratio of the (d-Glu)6 congener indicates that this MG analogue might be a good candidate for further clinical study. |
Formato |
application/pdf |
Identificador |
http://boris.unibe.ch/70210/1/acs%252Ebioconjchem%252E5b00187.pdf Kolenc Peitl, Petra; Tamma, MariaLuisa; Kroselj, Marko; Braun, Friederike; Waser, Beatrice; Reubi, Jean-Claude; Sollner Dolenc, Marija; Maecke, Helmut R; Mansi, Rosalba (2015). Stereochemistry of Amino Acid Spacers Determines the Pharmacokinetics of (111)In-DOTA-Minigastrin Analogues for Targeting the CCK2/Gastrin Receptor. Bioconjugate chemistry, 26(6), pp. 1113-1119. American Chemical Society 10.1021/acs.bioconjchem.5b00187 <http://dx.doi.org/10.1021/acs.bioconjchem.5b00187> doi:10.7892/boris.70210 info:doi:10.1021/acs.bioconjchem.5b00187 info:pmid:25971921 urn:issn:1043-1802 |
Idioma(s) |
eng |
Publicador |
American Chemical Society |
Relação |
http://boris.unibe.ch/70210/ |
Direitos |
info:eu-repo/semantics/restrictedAccess |
Fonte |
Kolenc Peitl, Petra; Tamma, MariaLuisa; Kroselj, Marko; Braun, Friederike; Waser, Beatrice; Reubi, Jean-Claude; Sollner Dolenc, Marija; Maecke, Helmut R; Mansi, Rosalba (2015). Stereochemistry of Amino Acid Spacers Determines the Pharmacokinetics of (111)In-DOTA-Minigastrin Analogues for Targeting the CCK2/Gastrin Receptor. Bioconjugate chemistry, 26(6), pp. 1113-1119. American Chemical Society 10.1021/acs.bioconjchem.5b00187 <http://dx.doi.org/10.1021/acs.bioconjchem.5b00187> |
Palavras-Chave | #570 Life sciences; biology #610 Medicine & health |
Tipo |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion PeerReviewed |