English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Evaluation of crotamine based probes as intracellular targeted contrast agents for magnetic resonance imaging

Joshi, R., Sweidan, K., Jha, D., Kerkis, I., Scheffler, K., & Engelmann, J. (2022). Evaluation of crotamine based probes as intracellular targeted contrast agents for magnetic resonance imaging. Bioorganic & Medicinal Chemistry, 69: 116863. doi:10.1016/j.bmc.2022.116863.

Item is

Basic

show hide
Genre: Journal Article

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Joshi, R, Author
Sweidan, K, Author              
Jha, D1, Author              
Kerkis, I, Author
Scheffler, K1, Author              
Engelmann, J1, Author              
Affiliations:
1Department High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497796              

Content

show
hide
Free keywords: -
 Abstract: Crotamine is a lysine and cysteine rich 42 amino acids long bio-active polypeptide, isolated from the venom of a South American rattlesnake, that also can be used as cell penetrating peptide. A facile synthetic scheme for coupling cargo molecules like fluorophores (carboxyfluorescein) or MRI probes (Gd-DO3A-based macrocycle) is presented. The toxicity, cellular internalization and steady-state accumulation after long-term incubation for 18 h, as well as magnetic resonance relaxivities and cellular relaxation rates of crotamine based probes were evaluated and compared to its shorter synthetic fragment CyLoP-1. The longitudinal relaxivity (r1) of the conjugates of CyLoP-1 and crotamine is significantly lower in medium than in water indicating to the lower contrast enhancement efficacy of DO3A-based probes in biological samples. Carboxyfluorescein labeled crotamine did not exhibit toxicity up to a concentration of 2.5 µM. CyLoP-1 accumulated about four times better within the cells compared to crotamine. Fluorescence microscopy suggests different predominant uptake mechanisms for crotamine and CyLoP-1 in 3T3 cells. While crotamine is predominantly localized in vesicular structures (most likely endosomes and lysosomes) within the cell, CyLoP-1 is mainly homogeneously distributed in the cytosol. The cellular relaxation rate (R1, cell) of the crotamine based probe was not significantly increased whereas the corresponding CyLoP-1-derivative showed a slightly elevated R1, cell. This study indicates the potential of crotamine and in particular the shorter fragment CyLoP-1 to be useful for an efficient transmembrane delivery of agents directed to intracellular (cytosolic) targets. However, the applicability of the conjugates synthesized here as contrast agents in MR imaging is limited. Further improvement is needed to prepare more efficient probes for MRI applications, i.e., by replacing the DO3A- with a DOTA-based chelate.

Details

show
hide
Language(s):
 Dates: 2022-062022-09
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/j.bmc.2022.116863
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Bioorganic & Medicinal Chemistry
  Other : Bioorg. Med. Chem.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Amsterdam, The Netherlands : Elsevier B. V.
Pages: 9 Volume / Issue: 69 Sequence Number: 116863 Start / End Page: - Identifier: ISSN: 0968-0896
CoNE: https://pure.mpg.de/cone/journals/resource/954925582193