Synthesis and 177 Lu Labeling of the First Retro Analog of the HER2-Targeting A9 Peptide: A Superior Variant.

Autor: Sharma AK; Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, Maharashtra 400085, India.; Homi Bhabha National Institute, Mumbai 400094, India., Sharma R; Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, Maharashtra 400085, India.; Homi Bhabha National Institute, Mumbai 400094, India., Das A; Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, Maharashtra 400085, India.; Homi Bhabha National Institute, Mumbai 400094, India., Chakraborty A; Radiation Medicine Centre, Bhabha Atomic Research Centre, Mumbai, Maharashtra 400012, India.; Homi Bhabha National Institute, Mumbai 400094, India., Rakshit S; Radiation Medicine Centre, Bhabha Atomic Research Centre, Mumbai, Maharashtra 400012, India., Sarma HD; Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, Maharashtra 400085, India., Mukherjee A; Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, Maharashtra 400085, India.; Homi Bhabha National Institute, Mumbai 400094, India., Das T; Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, Maharashtra 400085, India.; Homi Bhabha National Institute, Mumbai 400094, India., Satpati D; Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, Maharashtra 400085, India.; Homi Bhabha National Institute, Mumbai 400094, India.
Jazyk: angličtina
Zdroj: Bioconjugate chemistry [Bioconjug Chem] 2023 Sep 20; Vol. 34 (9), pp. 1576-1584. Date of Electronic Publication: 2023 Jun 28.
DOI: 10.1021/acs.bioconjchem.3c00265
Abstrakt: The retro analog of the HER2-targeting A9 peptide was synthesized by coupling amino acids in a reverse fashion and switching the N-terminal in the original sequence of the L-A9 peptide (QDVNTAVAW) to the C-terminal in rL-A9 (WAVATNVDQ). Modification in the backbone resulted in higher conformational stability of the retro peptide as evident from CD spectra. Molecular docking analysis revealed a higher HER2 binding affinity of [ 177 Lu]Lu-DOTA-rL-A9 than the original radiopeptide [ 177 Lu]Lu-DOTA-L-A9. Enormously enhanced metabolic stability of the retro analog led to significant elevation in tumor uptake and retention. SPECT imaging studies corroborated biodistribution results demonstrating a remarkably higher tumor signal for [ 177 Lu]Lu-DOTA-rL-A9. The presently studied retro probe has promising efficiency for clinical screening.
Databáze: MEDLINE
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