Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Mar 2;72(5):1675-80.
doi: 10.1021/jo062276g. Epub 2007 Feb 6.

Design, synthesis, and validation of a branched flexible linker for bioactive peptides

Martina E Bowen  1 , Yasunari Monguchi, Rajesh Sankaranarayanan, Josef Vagner, Lucinda J Begay, Liping Xu, Bhumasamudram Jagadish, Victor J Hruby, Robert J Gillies, Eugene A Mash
Affiliations

Design, synthesis, and validation of a branched flexible linker for bioactive peptides

Martina E Bowen et al. J Org Chem. .

Abstract

A branched flexible linker that incorporates a fluorescent dansyl moiety was synthesized and used to connect two high affinity NDP-alpha-MSH ligands or two low affinity MSH(4) ligands. The linker was incorporated into the conjugate by solid-phase synthesis. In vitro biological evaluations showed that potency of binding to the human melanocortin 4 receptor was not diminished for linker-ligand combinations relative to the corresponding ligand alone.

PubMed Disclaimer

Figures

Scheme 1
Scheme 1. Synthesis of Compound 17a
a Reagents and conditions: (a) acrylonitrile, CH3OH; (b) NaH, THF; (c) DMSO, (COCl)2, Et3N, CH2Cl2; (d) NaBH(OAc)3, ClCH2CH2Cl; (e) TsOH, aq CH3OH; (f) K2CO3, CH3OH; (g) H2, Rh/C, EtNH2, CH3OH; (h) dansyl chloride, Et3N, CH2Cl2; (i) HCl, Et2O, EtOAc, CH3OH; (j) NaOH, aq CH3OH, THF; (k) CF3CO2Et, CH3OH, Et3N.
Scheme 2
Scheme 2. Solid-Phase Synthesis of Compounds 2 and 4a
a Reagents and conditions: (a) piperidine; (b) Fmoc/t-Bu solid-phase synthesis (ref 15); (c) N-protected linker, HCTU, i-Pr2EtN, DMF; (d) THF/MeOH/N2H4 (70/15/15); (e) pyridine/Ac2O (90/10); (f) TFA/HSCH2CH2SH/PhSMe/H2O (91/3/3/3).
See this image and copyright information in PMC

References

    1. Gillies RJ, Hoffman JM, Lam KS, Menkens AE, Piwnica-Worms DR, Sullivan DC, Weissleder R. Molecular Imaging. 2005;4:98–103. - PubMed
    2. Gillies RJ, Hruby VJ. Expert Opin. Ther. Targets. 2003;7:137–139. - PubMed
    1. Handl HL, Vagner J, Han H, Mash E, Hruby VJ, Gillies RJ. Expert Opin. Ther. Targets. 2004;8:565–586. - PubMed
    1. Mammen M, Chio SK, Whitesides GM. Angew. Chem., Int. Ed. 1998;37:2754–2794. - PubMed
    2. Kiessling LL, Gestwicki JE, Strong LE. Curr. Opin. Chem. Biol. 2000;4:696–703. - PubMed
    1. Tron L, Szollosi J, Szabo G, Jr., Matyus L, Damjanovich S. Symp. Biol. Hung. 1984;26:307–328. Small molecule dimensions are on the order of ten angstroms, while the distance between receptors is on the order of tens to hundreds of angstroms. See:
    1. Maison W, Frangioni JV, Pannier N. Org. Lett. 2004;6:4567–4569. - PMC - PubMed
    2. Monguchi Y, Vagner J, Handl HL, Jana U, Begay LJ, Hruby VJ, Gillies RJ, Mash EA. Tetrahedron Lett. 2005;46:7589–7592.
    3. Semetey V, Moustakas D, Whitesides GM. Angew. Chem., Int. Ed. 2006;45:588–591. - PubMed
    4. Vagner J, Handl HL, Monguchi Y, Jana U, Begay LJ, Mash EA, Hruby VJ, Gillies RJ. Bioconjugate Chem. 2006;17:1545–1550. - PMC - PubMed

Publication types