| Order of amino acids in C-terminal cysteine-containing peptide-based chelators influences cellular processing and biodistribution of (99m)Tc-labeled recombinant Affibody molecules. | |
| | |
MedLine Citation:
|
PMID: 21573874 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Affibody molecules constitute a novel class of molecular display selected affinity proteins based on non-immunoglobulin scaffold. Preclinical investigations and pilot clinical data have demonstrated that Affibody molecules provide high contrast imaging of tumor-associated molecular targets shortly after injection. The use of cysteine-containing peptide-based chelators at the C-terminus of recombinant Affibody molecules enabled site-specific labeling with the radionuclide (99m)Tc. Earlier studies have demonstrated that position, composition and the order of amino acids in peptide-based chelators influence labeling stability, cellular processing and biodistribution of Affibody molecules. To investigate the influence of the amino acid order, a series of anti-HER2 Affibody molecules, containing GSGC, GEGC and GKGC chelators have been prepared and characterized. The affinity to HER2, cellular processing of (99m)Tc-labeled Affibody molecules and their biodistribution were investigated. These properties were compared with that of the previously studied (99m)Tc-labeled Affibody molecules containing GGSC, GGEC and GGKC chelators. All variants displayed picomolar affinities to HER2. The substitution of a single amino acid in the chelator had an appreciable influence on the cellular processing of (99m)Tc. The biodistribution of all (99m)Tc-labeled Affibody molecules was in general comparable, with the main difference in uptake and retention of radioactivity in excretory organs. The hepatic accumulation of radioactivity was higher for the lysine-containing chelators and the renal retention of (99m)Tc was significantly affected by the amino acid composition of chelators. The order of amino acids influenced renal uptake of some conjugates at 1 h after injection, but the difference decreased at later time points. Such information can be helpful for the development of other scaffold protein-based imaging and therapeutic radiolabeled conjugates. |
| | |
Authors:
|
Mohamed Altai; Helena Wållberg; Anna Orlova; Maria Rosestedt; Seyed Jalal Hosseinimehr; Vladimir Tolmachev; Stefan Ståhl |
Related Documents
:
|
21986664 - Electrically conductive hybrid nanofibers constructed with two amphiphilic salt compone... 6430854 - Inhibition of glucosamine-6-phosphate synthetase from bacteria by anticapsin. 16958524 - Design and concise synthesis of fully protected analogues of l-gamma-carboxyglutamic acid. 6192134 - Quantitation of the epsilon-(gamma-glutamyl)lysine cross-link using a high-speed amino ... 8401334 - Determination of halfcystine in proteins as cysteine from reducing hydrolyzates. 11502544 - Stability and compatibility of ceftazidime administered by continuous infusion to inten... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-5-15 |
Journal Detail:
|
Title: Amino acids Volume: - ISSN: 1438-2199 ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
|
Created Date: 2011-5-16 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9200312 Medline TA: Amino Acids Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Division of Biomedical Radiation Sciences, Department of Radiology, Oncology and Clinical Immunology, Rudbeck Laboratory, Uppsala University, 75185, Uppsala, Sweden. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Neurogenic differentiation of amniotic fluid stem cells.
Next Document: Metabolic profiling of cadmium-induced effects in one pioneer intertidal halophyte Suaeda salsa by N...