Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Editor

Personal info

View

About

Terms

Javascript disabled

Please enable Javascript support in your browser to use this application.

Instructions on how to enable JavaScript on different browsers can be found here: http://www.google.com/support/bin/answer.py?answer=23852.

[edit this page]

García-López, M.T. et al.

Analgesic dipeptides. VI.: Synthesis and structure-activity relationships of N-terminal modified analogues of the analgesic compounds H-Xaa-Trp(Nps)-OMe (Xaa=Lys, Orn, Arg).

In order to determine the influence of the N-terminal amino group of the dipeptide derivatives H-Xaa-Trp(Nps)-OMe[Xaa = Lys (2a), Orn (2b), Arg (2c)] on their antinociceptive effects, the syntheses of their corresponding deaminated, acetylated and dimethylated analogues have been achieved. Deamino and dimethyl analogues of 2a,b,6a,b, and 18a,b were prepared by coupling the corresponding N omega-Z- and N omega-Z-N alpha-Me2 amino acids with H-Trp-OMe, using the DCC/HOSu method, followed by sulfenylation of the resulting compounds and removal of the Z groups. Guanidylation of 6b and 18b provided the arginine analogues 6c and 18c, respectively. Ac-Xaa-Trp(Nps)-OMe [Xaa = Lys (11a), Orn (11b) were synthesized by acetylation of H-Xaa(Z)-Trp(Nps)-OMe with acetic anhydride, in the presence of 4-dimethylaminopyridine, and subsequent removal of the Z groups. Coupling of Ac-Arg-OH.HC1 with H-Trp-OMe, using the DCC/HOSu procedure, followed by sulfenylation of the resulting 8:3 diastereomeric mixture of L,L and L,D dipeptides afforded Ac-ambo-Arg-Trp(Nps)-OMe 11c+11d. The antinociceptive effects of 6a-c, 11a-d, and 18 a-c were evaluated after i.c.v. administration in mice. The N alpha-acetyl dipeptides 11 were found to exhibit a naloxone-reversible antinociceptive effects comparable with those of 2, while N-deaminated and N,N-dimethylated analogues were inactive.[1]

References

Analgesic dipeptides. VI.: Synthesis and structure-activity relationships of N-terminal modified analogues of the analgesic compounds H-Xaa-Trp(Nps)-OMe (Xaa=Lys, Orn, Arg). García-López, M.T., González-Muñiz, R., Harto, J.R., Molinero, M.T., del Río, J. Arch. Pharm. (Weinheim) (1989) [Pubmed]

Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenes Open Access Licence Privacy Policy Terms of Use apsburg

The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.