99566-27-5

Usage

InChI:InChI=1/C54H76N14O10/c1-32(2)28-41(66-47(72)36(55)29-33-14-6-3-7-15-33)50(75)67-42(31-35-18-10-5-11-19-35)51(76)64-39(23-25-45(57)70)53(78)68-27-13-21-43(68)52(77)63-38(22-24-44(56)69)49(74)62-37(20-12-26-61-54(59)60)48(73)65-40(46(58)71)30-34-16-8-4-9-17-34/h3-11,14-19,32,36-43H,12-13,20-31,55H2,1-2H3,(H2,56,69)(H2,57,70)(H2,58,71)(H,62,74)(H,63,77)(H,64,76)(H,65,73)(H,66,72)(H,67,75)(H4,59,60,61)/t36-,37-,38-,39-,40-,41-,42-,43-/m0/s1

Upstream product

• 35661-60-0 Fmoc-Leu-OH 
• 71989-31-6 Fmoc-Pro-OH 
• 35661-40-6 N-Fmoc L-Phe 
• 71989-20-3 N₂-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-glutamine 
• 91000-69-0 Fmoc-L-Arg-OH 
• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 
• 13726-85-7 Boc-Gln-OH 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 13836-37-8 Boc-Arg(Tos)-OH 

Relevant academic research and scientific papers

Pressor and tachycardic responses to intrathecal administration of neuropeptide FF in anesthetized rats

Neuropeptide FF (NPFF) belongs to a neuropeptide family including two precursors (pro-NPFFA and pro-NPFFB) and two receptors (NPFF1 and NPFF2). NPFF and NPFF receptor mRNAs have been reported to be highly expressed and localized in the rat and human spinal cord. In the present study, the i.t. action of NPFF system on blood pressure and heart rate were examined using NPFF and two related agonists, NPVF and dNPA, which exhibit highest selectivities for NPFF1 and NPFF2 receptors, respectively. In urethane-anesthetized rats, NPFF and related peptides (5-40 nmol, i.t.) produced significant pressor and tachycardic responses at the spinal cord level. These effects were dose-dependent and similar with respect to time-course for the three peptides. Furthermore, i.t. injection of RF9 (20 nmol), a selective NPFF antagonist, significantly antagonized the cardiovascular responses to 20 nmol NPFF and related peptides (i.t.). Moreover, pretreatment of the rats with α-adrenoceptor antagonist phentolamine (1 mg/kg, i.v.) significantly reduced the pressor effects of NPFF. Nevertheless, pretreatment with muscarinic receptor and adrenoceptor antagonists (i.v.) could block the tachycardic effects induced by NPFF. Collectively, our results suggested that i.t. administration of NPFF and related peptides increased MAP and HR which were possibly mediated by the activation of both NPFF1 and NPFF2 receptors in the rat spinal cord. In addition, our results showed that the muscarinic receptor and adrenoceptor participated in the tachycardic response to i.t. NPFF, while α-adrenoceptor played an important role in the regulation of pressor effect of NPFF.

Structure-activity study of neuropeptide FF: Contribution of N-terminal regions to affinity and activity

Twenty neuropeptide FF (NPFF) analogs having various lengths were synthesized by solid-phase peptide synthesis to gain more information on the role of N-terminal residues for the NPFF receptor affinity. The affinities were evaluated in the rat spinal cord membrane preparations, and the biological activities were measured on morphine analgesia in the mouse tail- flick test. Shortening of the NPFF sequence from the N-terminus produced only a moderate decrease in affinity until NPFF(4-8) was reached. In the same way, NPFF(3-8) significantly decreased morphine analgesia, while NPFF(4-8) had no significant effect at a dose of 22 nmol. The introduction in the N-terminal part of NPFF of a D-enantiomer at positions 2 and 1 or the presence of an N- methyl group on position 3 did not modify affinity and activity. Substitution of proline5 by the D-isomer decreased the affinity of NPFF analogs whatever their length, and [Tyr1,D-Pro5]NPFF(1-8) was 2.5-fold less potent than [Tyr1]NPFF(1-8) in reversing morphine-induced analgesia. In contrast, the presence of a glycine residue in position 5 did not influence the affinity toward NPFF receptors. Data provide evidence that the N-terminal segment of neuropeptide FF is responsible for high-affinity binding.