Peptoid-peptide hybrids as potent novel melanocortin receptor ligands.

Department of Medicinal Chemistry, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
Journal of Medicinal Chemistry (Impact Factor: 5.61). 07/2005; DOI: 10.1021/jm0490033
Source: OAI

ABSTRACT All possible peptoid-peptide hybrids of an MC4 receptor agonist were synthesized and investigated on cells expressing different melanocortin (MC) receptor subtypes and for rat grooming behavior. In general, receptor selectivity remained while affinity and potency were decreased. The length of the functional group of Trp was more important for MC3 and MC5 than for MC4 receptor binding. In general, the potency of the peptoid-peptide hybrids to increase rat excessive grooming behavior correlated well with MC4 receptor pharmacology.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: G protein-coupled receptors (GPCRs), which are involved in virtually every biological process, constitute the largest family of transmembrane receptors. Many top-selling and newly approved drugs target GPCRs. In this review, we aim to recapitulate efforts and progress in combinatorial library-assisted GPCR ligand discovery, particularly focusing on one-bead-one-compound library synthesis and quantum dot-labeled cell-based assays, which both effectively enhance the rapid identification of GPCR ligands with higher affinity and specificity.
    Future medicinal chemistry 05/2014; 6(7):809-23. · 3.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A study on the preparation of N-alkylglycines (peptoids) that contain tertiary amino residues on the N-alkyl side chains is reported. The appropriate combination of the submonomer strategy with N-alkylglycine monomer couplings depending upon the structure of the N-alkyl side chain that must be incorporated into the peptoid is determinant for the efficiency of the synthetic pathway. The application of this strategy to the preparation of SICHI, an N-alkyglycine trimer containing tertiary amino residues in the three N-alkyl branches, and that has been identified as a potent Semaphorin 3A inhibitor, is presented.Graphical abstract
    Tetrahedron. 01/2010; 66(13):2444-2454.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The fragmentation patterns of a group of doubly protonated ([P + 2H](2+)) and mixed protonated-sodiated ([P + H + Na](2+)) peptide-mimicking oligomers, known as peptoids, have been studied using electron capturing dissociation (ECD) tandem mass spectrometry techniques. For all the peptoids studied, the primary backbone fragmentation occurred at the N-Cα bonds. The N-terminal fragment ions, the C-ions (protonated) and the C'-ions (sodiated) were observed universally for all the peptoids regardless of the types of charge carrier. The C-terminal ions varied depending on the type of charge carrier. The doubly protonated peptoids with at least one basic residue located at a position other than the N-terminus fragmented by producing the Z(•)-series of ions. In addition, most doubly protonated peptoids also produced the Y-series of ions with notable abundances. The mixed protonated-sodiated peptoids fragmented by yielding the Z(•)'-series of ions in addition to the C'-series. Chelation between the sodium cation and the amide groups of the peptoid chain might be an important factor that could stabilize both the N-terminal and the C-terminal fragment ions. Regardless of the types of the charge carrier, one notable fragmentation for all the peptoids was the elimination of a benzylic radical from the odd-electron positive ions of the protonated peptoids ([P + 2H](•+)) and the sodiated peptoids ([P + H + Na](•+)). The study showed potential utility of using the ECD technique for sequencing of peptoid libraries generated by combinatorial chemistry.
    Journal of the American Society for Mass Spectrometry 05/2014; · 3.59 Impact Factor

Full-text (2 Sources)

Available from
Jun 10, 2014