1190366-68-7Relevant academic research and scientific papers
DEPBT as coupling reagent to avoid racemization in a solution-phase synthesis of a kyotorphin derivative
Ramu, Vasanthakumar G.,Bardaji, Eduard,Heras, Montserrat
, p. 1481 - 1486 (2014/06/10)
The synthesis of IbKTP-NH2 with reduction of racemization up to no detectable level has been achieved using 3-(diethoxyphosphoryloxy)-1,2,3- benzotriazin-4(3H)-one (DEPBT). Among all coupling systems tested, only DEPBT-mediated amide bond formation between Nα-acylated tyrosine and arginine without loss of optical purity. Georg Thieme Verlag Stuttgart New York.
Chemical conjugation of the neuropeptide kyotorphin and ibuprofen enhances brain targeting and analgesia
Ribeiro, Marta M. B.,Pinto, Antonia R. T.,Domingues, Marco M.,Serrano, Isa,Heras, Montserrat,Bardaji, Eduard R.,Tavares, Isaura,Castanho, Miguel A.
, p. 1929 - 1940 (2012/07/14)
The pharmaceutical potential of natural analgesic peptides is mainly hampered by their inability to cross the blood-brain barrier, BBB. Increasing peptide-cell membrane affinity through drug design is a promising strategy to overcome this limitation. To address this challenge, we grafted ibuprofen (IBP), a nonsteroidal anti-inflammatory drug, to kyotorphin (l-Tyr-l-Arg, KTP), an analgesic neuropeptide unable to cross BBB. Two new KTP derivatives, IBP-KTP (IbKTP-OH) and IBP-KTP-amide (IbKTP-NH2), were synthesized and characterized for membrane interaction, analgesic activity and mechanism of action. Ibuprofen enhanced peptide-membrane interaction, endowing a specificity for anionic fluid bilayers. A direct correlation between anionic lipid affinity and analgesic effect was established, IbKTP-NH2 being the most potent analgesic (from 25 μmol·kg-1). In vitro, IbKTP-NH 2 caused the biggest shift in the membrane surface charge of BBB endothelial cells, as quantified using zeta-potential dynamic light scattering. Our results suggest that IbKTP-NH2 crosses the BBB and acts by activating both opioid dependent and independent pathways.
