Improvement of the pharmacological properties of amidated kyotorphin by means of iodination

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Oliveira, MC (Author) Other; Gano, L (Author) Other; Santos, I (Author) Other; Correia, JDG (Author) Other; Serrano, ID (Author) Other; Santos, SS (Author) Other; Ribeiro, M (Author) Other; Perazzo, J (Author) Other; Isaura Tavares (Author) FMUP; Heras, M (Author) Other; Bardaji, E (Author) Other; Castanho, MA (Author) Other

Journal

Title: MedChemComm

Vol. 7

Pages: 906-913

ISSN: 2040-2503

Publisher: Royal Society of Chemistry

Indexing

ISI Web of Knowledge - 3 Citations

Scopus - 3 Citations

Other information

Authenticus ID: P-00K-GVV

DOI: 10.1039/c6md00028b

Abstract (EN): Amidated kyotorphin (L-Tyr-L-Arg-NH2; KTP-NH2) shows analgesic properties following systemic administration. Although KTP-NH2 does not have toxic effects in the liver, its biodistribution is unknown. KTP-NH2 was radioiodinated to evaluate its biological fate in vivo. Mono-radioiodinated KTP-NH2 ([I-125]MIK) was radiochemically stable in vitro, namely in saline at 4 degrees C up to 1 week, and moderately stable when incubated with human serum at 37 degrees C. Although the radioiodinated peptide could translocate a cellular model of the blood-brain barrier (BBB), the levels of radioactivity in the brain were minimal, 5 and 10 min after intraperitoneal injection (i.p.). Significant accumulation of I-125 was found in the thyroid probably reflecting the hydrolysis of the iodine-tyrosine bond by liver deiodinases. HPLC analysis of plasma samples collected 5 min post-injection showed that intact [I-125]MIK accounted for 72.5% of the total radioactivity, whereas the remaining radioactivity was associated with free radioiodide (I-). These findings were subsequently confirmed by the low radioactivity found in the liver and kidney homogenates from rats sacrificed 10 min after i.p. administration. The analgesic activity of mono-and di-iodinated KTP-NH2 was also evaluated by a hot plate assay showing a delayed peak of maximal efficacy compared to KTP-NH2 (30 vs. 15 minutes). Overall, the peripheral effects of the peptides cannot be excluded.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8