Solid phase synthesis of a redox delivery system with the aim of targeting peptides into the brain.
A solid phase approach for the preparation of peptides attached to a redox chemical delivery system derived from stable annulated NADH models is reported. The synthesis starts with the grafting on a Merrifield resin of quinoline 4b, precursor of the redox carrier. From the resulting quinoline supported resin 4d, the stepwise SPPS of both octapeptide OP (RPGLLDLK) and octadecaneuropeptide ODN (QATVGDVNTDRPGLLDLK), two neuropeptides exhibiting anorexigenic effects, was successfully achieved by conventional methods. Quaternization of the quinoline moiety prior to cleavage of the modified OP and ODN peptides from the resin, led to the expected quinolinium salt 8a and 8b respectively linked to OP or ODN peptides. Finally, the reduction with NaBH4 monitored by UV-vis, provided the desired annulated NADH models as peptides carriers with either the OP (11a,b) or ODN (12a,b) moiety.
Laboratoire de Chimie Fine et Hétérocyclique UMR 6014 IRCOF, CNRS, Université et INSA de Rouen, BP 08, 76131 Mont-Saint-Aignan Cédex, France.
Claudine
C
Patteux
Lénaïg
L
Foucout
Pierre
P
Bohn
Georges
G
Dupas
Jérôme
J
Leprince
Marie-Christine
MC
Tonon
Bénédicte
B
Dehouck
Francis
F
Marsais
Cyril
C
Papamicaël
Vincent
V
Levacher
D000595:Amino Acid Sequence; D001671:Biochemistry / Q000379:methods*; D001894:Borohydrides / Q000737:chemistry; D001921:Brain / Q000187:drug effects; D004095:Dihydropyridines / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D009479:Neuropeptides / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism; D010084:Oxidation-Reduction; D011804:Quinolines / Q000737:chemistry; D011806:Quinolinium Compounds / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet
D001894:Borohydrides; D004095:Dihydropyridines; D009479:Neuropeptides; D011804:Quinolines; D011806:Quinolinium Compounds; D009243:NAD; C038806:1,4-dihydropyridine; C025364:sodium borohydride; C037219:quinoline