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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2016

Autores

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

Revista

Título: MedChemComm

Vol. 7

Páginas: 906-913

ISSN: 2040-2503

Editora: Royal Society of Chemistry

Indexação

ISI Web of Knowledge - 3 Citações

Scopus - 3 Citações

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 8